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Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas
This phase II trial studies how well nivolumab with or without varlilumab works in treating
patients with aggressive B-cell lymphomas that have come back or do not respond to treatment.
Immunotherapy with monoclonal antibodies, such as varlilumab and nivolumab, may help the
body's immune system attack the cancer, and may interfere with the ability of tumor cells to
grow and spread.
• Patients must have a histopathologically confirmed diagnosis of an aggressive B-cell
non-Hodgkin lymphoma that is recurrent or refractory to standard therapy
• For the purpose of this study, aggressive B-cell NHL will be deemed any lymphoma
belonging to one of the following groups according to the 2016 revision of the World
Health Organization (WHO) classification of lymphoid neoplasms
• For the purposes of stratification, diagnoses are grouped into 2 categories:
• Category A
• Burkitt lymphoma
• Burkitt-like lymphoma with 11q aberration
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6
rearrangements
• High-grade B-cell lymphoma, not otherwise specified (NOS)
• Category B
• Diffuse large B-cell lymphoma (DLBCL), NOS
• Diffuse large B-cell lymphoma (DLBCL), NOS; germinal center B-cell type
• Diffuse large B-cell lymphoma (DLBCL), NOS; activated B-cell type
• Large B-cell lymphoma with IRF4 rearrangement
• T-cell/histiocyte-rich large B-cell lymphoma
• Primary DLBCL of the central nervous system (CNS)
• Primary cutaneous DLBCL, leg type
• Epstein-Barr virus (EBV)+ DLBCL, NOS
• EBV+ mucocutaneous ulcer
• DLBCL associated with chronic inflammation
• Lymphomatoid granulomatosis
• Primary mediastinal (thymic) large B-cell lymphoma
• Intravascular large B-cell lymphoma
• ALK+ large B-cell lymphoma
• Plasmablastic lymphoma
• Primary effusion lymphoma
• Human herpesvirus (HHV)-8+ DLBCL, NOS
• B-cell lymphoma, unclassifiable, with features intermediate between
DLBCL and classical Hodgkin lymphoma
• Patients must have measurable disease, defined as at least one lesion that is > 15 mm
(1.5 cm) in the longest axis on cross-sectional imaging and measurable in two
perpendicular dimensions per computed tomography (spiral computed tomography [CT]),
positron emission tomography (PET)-CT or magnetic resonance imaging (MRI)
• Patients must have disease that has relapsed after or is refractory to at least 2
lines of standard therapy; the remaining standard treatment options are unlikely to be
effective in the opinion of the treating physician, or patient is felt to be
ineligible for such therapies or the patient refuses such therapies; patients who have
undergone autologous stem cell transplant are eligible as long as they meet all other
criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of greater than 12 weeks
• White blood cell (WBC) >= 2000/mm^3 (within 14 days of registration)
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of registration)
• Platelet count >= 100,000/mm^3 (within 14 days of registration)
• Hemoglobin > 9.0 g/dL (within 14 days of registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except patients with Gilbert
Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 14 days of registration)
• Aspartate transaminase (aspartate aminotransferase [AST]) =< 2.5 x ULN (within 14 days
of registration)
• Calculated creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault
formula) (within 14 days of registration)
• Females of child bearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
[HCG])
• Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
• Patient has received chemotherapy, targeted agent, or radiotherapy within 4 weeks or
at least 5 half-lives, whichever is longer, prior to registration
• Palliative (limited-field) radiation therapy is permitted, if all of the following
criteria are met:
• Repeat imaging demonstrates no new sites of bone metastases
• The lesion being considered for palliative radiation is not a target lesion
• Patient has received immunotherapy (including monoclonal antibodies) within 4 weeks
prior to registration
• Patients who have not recovered to grade 1 or less from any adverse events due to
agents administered more than 4 weeks earlier (excluding alopecia)
• Patients who are receiving any other investigational agents
• Patients should be excluded if they have had prior treatment with an anti-PD-1,
anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Patients who have received autologous stem cell transplant (ASCT) =< 12 weeks prior to
the first dose of study drug
• Patients with a prior history of allogeneic stem cell or solid organ transplantation
• Patients with evidence of active disease in the central nervous system (CNS) defined
as either the presence of active lesions on MRI obtained within 4 weeks of
registration or progressive neurological decline
• Patients with primary CNS lymphoma who develop systemic recurrence following
standard therapy may be included as long as no active CNS disease is present at
the time or enrollment; similarly, patients with secondary involvement of the CNS
from a systemic lymphoma may be included as long as the CNS disease has been
optimally treated and they demonstrate no evidence of active CNS disease
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CDX-1127 (varlilumab) and/or nivolumab
• History of severe hypersensitivity reaction to any monoclonal antibody
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
• Pregnant women are excluded from this study because CDX-1127 (varlilumab) and
nivolumab are agents with the potential for teratogenic or abortifacient effects;
because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with CDX-1127 (varlilumab) or nivolumab,
breastfeeding should be discontinued if the mother is treated with CDX-1127
(varlilumab) or nivolumab
• Patients with human immunodeficiency virus (HIV) are eligible for the study provided
they meet the other protocol criteria in addition to the following:
• Undetectable HIV load by standard polymerase chain reaction (PCR) clinical assay
within 60 days prior to registration
• Absolute CD4 count of >= 200 mm^3 within 60 days prior to registration
• Willing to maintain adherence to combination antiretroviral therapy
• No history of acquired immunodeficiency syndrome (AIDS) defining condition (other
than lymphoma or CD4 cell count < 200 mm^3)
• Likely to have near normal lifespan if not for the presence of
relapsed/refractory lymphoma
• Patients with evidence of hepatitis B virus (HBV) are eligible provided
there is minimal hepatic injury and the patient has undetectable HBV on
suppressive HBV therapy; patient must be willing to maintain adherence to
HBV therapy
• Patients with previously treated and eradicated hepatitis C virus (HCV) who
have minimal hepatic injury are eligible
• Patients with active autoimmune disease or history of autoimmune disease that might
recur, which may affect vital organ function or require immune suppressive treatment
including systemic corticosteroids, should be excluded; these include but are not
limited to patients with a history of immune related neurologic disease, multiple
sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia
gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE),
connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's,
ulcerative colitis, hepatitis; and patients with a history of toxic epidermal
necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be
excluded because of the risk of recurrence or exacerbation of disease; patients with
vitiligo, endocrine deficiencies including thyroiditis managed with replacement
hormones including physiologic corticosteroids are eligible; patients with rheumatoid
arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with
topical medication and patients with positive serology, such as antinuclear antibodies
(ANA), anti-thyroid antibodies should be evaluated for the presence of target organ
involvement and potential need for systemic treatment but should otherwise be eligible
• Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,
residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger (precipitating event)
• Patients should be excluded if they have a condition requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration; inhaled or
topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents
are permitted in the absence of active autoimmune disease; patients are permitted to
use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids
(with minimal systemic absorption); physiologic replacement doses of systemic
corticosteroids are permitted, even if =< 10 mg/day prednisone equivalents; a brief
course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for
treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction
caused by contact allergen) is permitted
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal
abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are
known risk factors for bowel perforation should be evaluated for the potential need
for additional treatment before coming on study
• Patients with other active malignancy =< 3 years prior to registration for which
active treatment is required must be excluded; patients with composite lymphomas that
have a non-B-cell component must be excluded EXCEPTIONS: Non-melanotic skin cancer or
carcinoma-in-situ of the cervix
Biological: Nivolumab, Drug: Varlilumab
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Plasmablastic Lymphoma, ALK-Positive Large B-Cell Lymphoma, Atypical Burkitt/Burkitt-Like Lymphoma, Burkitt-Like Lymphoma With 11q Aberration, Diffuse Large B-Cell Lymphoma Activated B-Cell Type, Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation, Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Mucocutaneous Ulcer, Human Herpesvirus 8-Positive Neoplastic Cells Present, Intravascular Large B-Cell Lymphoma, Large B-Cell Lymphoma With IRF4 Rearrangement, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System, Primary Effusion Lymphoma, Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma, Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Burkitt Lymphoma, Recurrent Lymphomatoid Granulomatosis, Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma, Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Burkitt Lymphoma, Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma, Small Intestinal High Grade B-Cell Lymphoma, Not Otherwise Specified, T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, High Grade B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
A Study to Determine the Outcomes of Patients With Localized B Cell Lymphoblastic Lymphoma (B-LLy) When Treated With Standard Risk B-ALL Therapy
This phase III trial studies how well blinatumomab works in combination with chemotherapy in
treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or
B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as
blinatumomab, may induce changes in body's immune system and may interfere with the ability
of cancer cells to grow and spread. Drugs used in chemotherapy, such as vincristine,
dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine,
mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to
stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate.
Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving
blinatumomab and combination chemotherapy may work better then combination chemotherapy alone
in treating patients with B-ALL. This trial also assigns patients into different chemotherapy
treatment regimens based on risk (the chance of cancer returning after treatment). Treating
patients with chemotherapy based on risk may help doctors decide which patients can best
benefit from which chemotherapy treatment regimens.
• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening
(Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement
for B-LLy patients. B-LLy patients may directly enroll on AALL1731 and MUST submit
eligibility studies.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or
without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL
(performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell
count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on
a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis
can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without
Down syndrome.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion
for diagnosis should be analogous to B-ALL. For tissue processed by other means
(i.e., paraffin blocks), the methodology and criteria for immunophenotypic
analysis to establish the diagnosis of B-LLy defined by the submitting
institution will be accepted (diagnostic biopsy for B-LLy must be performed
within 14 days prior to enrollment).
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
Exclusion Criteria:
• Patient must not have secondary ALL that developed after treatment of a prior
malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior
history of transient myeloproliferative disease (TMD) are not considered to have had a
prior malignancy. They would therefore be eligible whether or not the TMD was treated
with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for
either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to
initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion
criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in
the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to
initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV
steroids within 4 weeks of diagnosis.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for
APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be
known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the
DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior
to administration of any systemic or intrathecal chemotherapy, except for steroid
pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular
disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, the following additional exclusion criteria apply:
• T-Lymphoblastic Lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• CNS positive disease or testicular involvement.
• M2 (5% •25% blasts) or M3 (> 25% blasts) marrow.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with evidence of a MYC translocation associated with mature (Burkitt) B-cell
ALL, regardless of blast immunophenotype.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
This phase II MATCH trial studies how well treatment that is directed by genetic testing
works in patients with solid tumors or lymphomas that have progressed following at least one
line of standard treatment or for which no agreed upon treatment approach exists. Genetic
tests look at the unique genetic material (genes) of patients' tumor cells. Patients with
genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more
from treatment which targets their tumor's particular genetic abnormality. Identifying these
genetic abnormalities first may help doctors plan better treatment for patients with solid
tumors, lymphomas, or multiple myeloma.
• ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)
• Women of childbearing potential must have a negative serum pregnancy test within 2
weeks prior to registration; patients that are pregnant or breast feeding are
excluded; a female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 4 months after completion of study;
should a woman become pregnant or suspect while she or her partner is participating in
this study, she should inform her treating physician immediately
• Patients must have histologically documented solid tumors or histologically confirmed
diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the
following criteria:
• Patients must have progressed following at least one line of standard systemic
therapy and there must not be other approval/standard therapy available that has
been shown to prolong overall survival (i.e. in a randomized trial against
another standard treatment or by comparison to historical controls); patients who
cannot receive other standard therapy that has been shown to prolong overall
survival due to medical issues will be eligible, if other eligibility criteria
are met; if the patient is currently receiving therapy, the clinician must have
assessed that the current therapy is no longer benefitting the patient prior to
enrolling on MATCH, regardless of whether it is considered standard OR
• Patients for whose disease no standard treatment exists that has been shown to
prolong overall survival
• NOTE: No other prior malignancy is allowed except for the following:
• Adequately treated basal cell or squamous cell skin cancer
• In situ cervical cancer
• Adequately treated stage I or II cancer from which the patient is currently in
complete remission
• Any other cancer from which the patient has been disease-free for 5 years
• Patients must have measurable disease
• Patients must meet the criteria below and have received results from one of the
designated outside laboratories indicating a "rare variant" that is an actionable
Mutation of Interest (aMOI) for specific select subprotocols.
• The following requirements apply:
• The outside laboratory specifically notified the site that patient may be a
potential candidate for MATCH due to a detected "rare variant"; the outside
lab reports are NOT sufficient for this purpose
• NOTE: The content and format of these specific notifications for the
Outside Assay process will vary depending on the designated outside lab
in question, as they are each responsible for their own outreach
efforts; it is strongly recommended that the designated outside
laboratory be contacted to confirm the format and receipt of this
notification prior to registering any patients to Step 0
• Patients with an applicable "rare variant" must be able to meet the
eligibility criteria for the appropriate subprotocols within 4 weeks
following notification of treatment assignment
• NOTE: The receipt of this notification (and the start of the associated
deadline for Step 1 registration) may occur shortly after Step 0
registration, since these patients will not be submitting tissue for
screening purposes; however, for certain "rare variant" arms,
submission of archival tissue for central immunohistochemistry (IHC)
testing may be required
• Registration to Step 0 must occur after stopping prior systemic anti-cancer
therapy; there is no specific duration for which patients must be off
treatment prior to registration to Step 0, as long as all eligibility
criteria are met
• There is no particular window of time after notification of potential
eligibility from an outside lab in which the patient must be registered to
Step 0, but treatment slots will be assigned on a first come, first serve
basis to those who do register to Step 0, and are not held for those
notified of potential eligibility who do not register to Step 0
• Patients may have received other non-targeted, immunotherapy or targeted
treatment between the prior genetic testing at the outside lab and
registration to Step 0; the decision to stop such treatment in favor of
participation in MATCH, if no further clinical benefit is expected, is per
the treating physician's discretion; documentation of a lack of response to
the prior treatment is not required in these cases
• NOTE: Other potential aMOIs that would be eligibility criteria for "NON
RARE" arms, as determined by the designated laboratories, are not
applicable for this process in MATCH
• NOTE: Tumor tissue for the confirmation of "rare variant" by the MATCH
assay is to be submitted, preferably from the same time of collection
as that evaluated by the designated outside laboratory
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
and a life expectancy of at least 3 months
• Patients must be able to swallow tablets or capsules; a patient with any
gastrointestinal disease that would impair ability to swallow, retain, or absorb drug
is not eligible
• Patients who are human immunodeficiency virus (HIV)-positive are eligible if:
• CD4+ cell count greater or equal to 250 cells/mm^3
• If patient is on antiretroviral therapy, there must be minimal interactions or
overlapping toxicity of the antiretroviral therapy with the experimental cancer
treatment; for experimental cancer therapeutics with CYP3A/4 interactions,
protease inhibitor therapy is disallowed; suggested regimens to replace protease
inhibitor therapy include dolutegravir given with tenofovir/emtricitabine;
raltegravir given with tenofovir and emtricitabine; once daily combinations that
use pharmacologic boosters may not be used
• No history of non-malignancy acquired immune deficiency syndrome (AIDS)-defining
conditions other than historical low CD4+ cell counts
• Probable long-term survival with HIV if cancer were not present
• Any prior therapy, radiotherapy (except palliative radiation therapy of 30 gray [Gy]
or less), or major surgery must have been completed >= 4 weeks prior to start of
treatment; all adverse events due to prior therapy have resolved to a grade 1 or
better (except alopecia and lymphopenia) by start of treatment; palliative radiation
therapy must have been completed at least 2 weeks prior to start of treatment; the
radiotherapy must not be to a lesion that is included as measurable disease
• NOTE: Prostate cancer patients may continue their luteinizing hormone-releasing
hormone (LHRH) agonist
• NOTE: For patients entering the study via the original screening process,
patients may receive non-protocol treatment after biopsy (if clinically
indicated) until they receive notification of results; however, lack of response
must be documented prior to registration to Step 1; new non-protocol treatment
will NOT be permitted as intervening therapy after registration to Step 0; the
only intervening treatment permitted is prior therapy that the patient already
received prior to Step 0 registration; the decision to stop the intervening
non-protocol treatment will be left up to the treating physician if patient has
an aMOI; however, patients will need to be off such therapy for at least 4 weeks
before receiving any MATCH protocol treatment
• NOTE: For patients entering the study via a designated outside laboratory, no
intervening systemic non-protocol treatment is permitted after Step 0
registration; all other eligibility requirements still apply to these patients,
including the washouts for prior therapy noted above in this section, the time
restrictions outlined, and the eligibility criteria for the intended subprotocol
• Patients with brain metastases or primary brain tumors must have completed treatment,
surgery or radiation therapy >= 4 weeks prior to start of treatment
• Patients must have discontinued steroids >= 1 week prior to registration to Step 0 and
remain off steroids thereafter, except as permitted; patients with glioblastoma (GBM)
must have been on stable dose of steroids, or be off steroids, for one week prior to
registration to treatment (Step 1, 3, 5, 7)
• NOTE: The following steroids are permitted (low dose steroid use is defined as
prednisone 10 mg daily or less, or bioequivalent dose of other corticosteroid):
• Temporary steroid use: e.g. for computed tomography (CT) imaging in setting
of contrast allergy
• Low dose steroid use for appetite
• Chronic inhaled steroid use
• Steroid injections for joint disease
• Stable dose of replacement steroid for adrenal insufficiency or low doses
for non-malignant disease
• Topical steroid
• Steroids required to manage toxicity related to study treatment, as
described in the subprotocols
• Steroids required as pre- or post-chemotherapy medication for acceptable
intervening chemotherapy
• NOTE: Steroids must be completed alongside last dose of chemotherapy
• Leukocytes >= 3,000/mcL (within 2 weeks prior to screening step registration and
within 4 weeks prior to treatment step registration)
• Absolute neutrophil count >= 1,500/mcL (within 2 weeks prior to screening step
registration and within 4 weeks prior to treatment step registration)
• Platelets >= 100,000/mcL (within 2 weeks prior to screening step registration and
within 4 weeks prior to treatment step registration)
• NOTE: Patients with documented bone marrow involvement by lymphoma are not required to
meet the above hematologic parameters, but must have a platelet count of at least
75,000/mcL and neutrophil count of at least 1,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless documented
Gilbert's syndrome, for which bilirubin =< 3 x institutional ULN is permitted) (within
2 weeks prior to screening step registration and within 4 weeks prior to treatment
step registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (up to 5 times ULN in presence of liver metastases) (within
2 weeks prior to screening step registration and within 4 weeks prior to treatment
step registration)
• Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above
institutional normal
• As defined by the Cockcroft-Gault equation (within 2 weeks prior to screening
step registration and within 4 weeks prior to treatment step registration)
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to
screening step and must meet the following cardiac criteria:
• Resting corrected QT interval (QTc) =< 480 msec
• NOTE: If the first recorded QTc exceeds 480 msec, two additional,
consecutive ECGs are required and must result in a mean resting QTc =< 480
msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks
between the ECGs
• The following only need to be assessed if the mean QTc > 480 msec
• Check potassium and magnesium serum levels
• Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG
to confirm exclusion of patient due to QTc
• For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual
read of QTc is required
• For patients with baseline HR < 60 or > 100 bpm, manual read of QT by
trained personnel is required, with Fridericia correction applied to
determine QTc
• Patient must not have hypokalemia (value < institutional lower limit of
normal)
• No factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, congenital long QT syndrome, family history of long
QT syndrome or unexplained sudden death under 40 years of age or any concomitant
medication known to prolong the QT interval
• NOTE: Patient must be taken off prohibited medication prior to registration
to the screening step (Step 0, 2, 4, 6) and remain off these medications
thereafter, unless permitted on a subprotocol for the management of
treatment related toxicity; patient must be off the drug for at least 5
half-lives prior to registration to the treatment step (Step 1, 3, 5, 7);
the medication half-life can be found in the package insert for Food and
Drug Administration (FDA) approved drugs
• ELIGIBILITY CRITERIA FOR FIRST TREATMENT (STEP 1)
• If patients have been biopsied or submitted archived tumor tissue obtained within the
last 6 months for assessment with the MATCH assays, patients may receive non-protocol
treatment after biopsy/tissue submission (if clinically indicated) until they receive
notification of results however, lack of response must be documented prior to
registration to step 1; new non-protocol treatment will NOT be permitted as
intervening therapy after registration to Step 0; for patients entering step 0 with
assay results from outside laboratories, no systemic treatment is allowed after step 0
registration; the decision to stop the intervening nonprotocol treatment will be left
up to the treating physician if patient has an aMOI; waiting periods as described will
apply
• As MATCH is designed to add additional subprotocols, implement limited expansions of
accrual for certain subprotocols, and/or amend existing arm-specific eligibility
criteria, some patients entering under the original screening method may be eligible
to have their results rerun in MATCHbox, even if they did not match to a treatment
initially or did not receive a treatment assignment due to a lack of available
assignment slots; patients whose sequence results will be rerun through MATCHbox must
also meet the following criteria:
• Samples must have been collected within 5 months of the activation of the
addendum, as there is an additional month needed to get the patients on trial
• Patient has not had treatment within the 5 months that resulted in a PR or better
after the performance of the screening assessment
• Patient must meet eligibility criteria, including performance status 1 or better
and life expectancy of at least 3 months
• Patients must meet the eligibility requirements with the following exceptions:
• Patients may have received other non-targeted, immunotherapy or targeted
treatment, which could be stopped in favor of returning to MATCH, if no
response to the interim treatment has occurred and no further benefit is
expected from this interim treatment, per the treating physician's
discretion; documentation o
Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
The purpose of the study is to determine the maximum tolerated dose and assess the safety,
tolerability and activity of carfilzomib, alone and in combination with induction
chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (ALL).
1. Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year at the
time of study treatment initiation.
2. Subjects must have a diagnosis of relapsed or refractory ALL with ≥ 5% blasts in the
bone marrow (M2 or M3 disease), with or without extramedullary disease.
a. To be eligible, subjects must have had 1 or more prior therapeutic attempts,
defined as:
• Early first relapse (< 36 months from original diagnosis) after achieving a CR
(B-ALL) or first relapse any time following the original diagnosis after
achieving a CR (T-ALL)
• First refractory bone marrow relapse occurring any time after original diagnosis
after achieving a CR (ie, ≥1 failed attempt to induce a second remission) OR
• Relapse after achieving a CR following the first or subsequent relapse (i.e., ≥ 2
relapses) OR
• Failing to achieve a CR from original diagnosis after at least 1 induction
attempt
3. Subjects must have fully recovered from the acute toxic effects of all previous
chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
4. Subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper limit
of normal (ULN) according to age. If serum creatinine level is > 1.5 × ULN, the
subject must have a calculated creatinine clearance or radioisotope glomerular
filtration rate (GFR) ≥ 70 mL/min/1.73 m2, or for children<2 years of age, ≥
50mL/min/1.73 m2.
5. Adequate liver function, defined as both of the following:
1. Total bilirubin ≤ 1.5 × institutional ULN except in the presence of Gilbert
Syndrome
2. Alanine aminotransferase (ALT) ≤ 5 × institutional ULN
6. Performance status: Karnofsky or Lansky scores ≥ 50 for subjects > 16 years old or ≤
16 years old, respectively.
Key
Exclusion Criteria:
1. Known allergy to any of the drugs used in the study. (Subjects who have had a previous
allergy to PEG-asparaginase are eligible and if able, may receive Erwinia asparaginase
at the investigator's discretion.)
2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
3. Left ventricular fractional shortening < 30%
4. History of ≥ Grade 2 pancreatitis
5. Active graft‑versus‑host disease requiring systemic treatment
6. Positive culture for or other clinical evidence of infection with bacteria or fungus
within 14 days of the initiation of study treatment
7. Down Syndrome
8. Prior therapy restrictions:
1. Subjects must have completed therapy with granulocyte‑colony stimulating factor
(G‑CSF) or other myeloid growth factors at least 7 days before study treatment
initiation, or at least 14 days before study treatment initiation, if pegylated
myeloid growth factors were administered.
2. Subjects must have completed any type of active immunotherapy (e.g., tumor
vaccines) at least 42 days before study treatment initiation.
3. Subjects must have received the last dose of a non-monoclonal antibody biologic
agent at least 7 days before study treatment initiation.
4. At least 3 antibody half‑lives must have elapsed since the last dose of
monoclonal antibody (e.g., 66 days for rituximab, 69 days for epratuzumab and 36
days for inotuzumab) before subjects may initiate study treatment.
5. Subjects must not have received other antineoplastic agents with therapeutic
intent, excluding hydroxyurea and antimetabolites administered as part of
maintenance chemotherapy, within 7 days prior to study treatment initiation
9. Hepatitis B infection with positive hepatitis B DNA
Study of UCART19 in Pediatric Patients With Relapsed/Refractory B Acute Lymphoblastic Leukemia (PALL)
This study aims to evaluate the safety and feasibility of UCART19 to induce molecular
remission in pediatric patients with relapsed or refractory CD19-positive B-cell acute
lymphoblastic leukemia (B-ALL).
• Patient with relapsed or refractory CD19-positive B-acute lymphoblastic leukaemia
(B-ALL) who have exhausted alternative treatment options.
• Estimated life expectancy ≥ 12 weeks
• Lansky (age < 16 years at the time of assent/consent) or Karnofsky (age ≥ 16 years at
time of assent/consent) performance status ≥ 50
Exclusion Criteria:
• Burkitt leukemia
• CD19-negative B-cell leukemia
• Active Central Nervous System (CNS) leukemia
• Active acute or chronic Graft-versus-Host Disease (GvHD) requiring systemic use
therapy within 4 weeks before UCART19 infusion
• Patients with autoimmune disease requiring systemic immunosuppression therapy that
cannot be stopped
• History of CRS grade 4 related to previous CAR T cell therapy
Tranexamic Acid for Prevention of Hemorrhage in Cesarean Delivery (TXA)
The investigators prepared a novel study of tranexamic acid (TXA) designed to estimate the
quantity of blood loss in women undergoing elective repeat cesarean deliveries. This is the
first trial to utilize a prophylactic dose of TXA prior to incision followed by a subsequent
prophylactic dose at placental delivery in obstetric patients undergoing scheduled cesareans.
The purpose of this study is to quantify blood loss during uncomplicated repeat cesarean
deliveries with and without TXA. The central hypothesis is that TXA administration reduces
blood loss and fibrinolysis in women undergoing repeat cesarean sections.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Olutoyosi Ogunkua
138932
Female
18 Years and over
Phase 2/Phase 3
This study is also accepting healthy volunteers
NCT03856164
STU-2018-0315
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Intrauterine pregnancy
2. Age ≥ 18
3. Gestation age ≥ 37 weeks 0 days
4. Scheduled cesarean delivery
5. Second or third cesarean delivery
6. Singleton pregnancy
Exclusion Criteria:
1. First cesarean delivery
2. Four or more cesarean deliveries
3. Intrauterine fetal death
4. Fetal anomalies
5. Documented coagulopathy (Elevated Prothrombin Time (PT), Elevated Partial
Thromboplastin Time (PTT), Elevated International Normalized Ratio (INR))
6. Thrombocytopenia (Platelet count < 100k)
7. Internal bleeding, external bleeding, easy bruising
8. History of thrombotic event
9. Hypertension
10. Diagnosis of renal insufficiency (Creatinine> 1 mg/dL)
11. Insulin-treated diabetes
12. Suspected morbidly adherent placenta
13. Placenta previa
14. Multiple Gestations
15. BMI ≥ 50
16. Hematocrit ≤ 25
17. Blood transfusion within 24 hours prior to cesarean delivery
18. History of abnormal bleeding or blood disorder
19. Planned general anesthesia
Drug: Tranexamic Acid, Drug: Placebo
Blood Loss, Post Partum Hemorrhage, Fibrinolysis, Hemorrhage
An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma (KarMMa-2)
This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy
and safety of bb2121 in subjects with relapsed and refractory MM (Cohort 1), in subjects with
MM having progressed within one 18 months of initial treatment including autologous stem cell
transplantation (ASCT) (Cohort 2a), and without ASCT (Cohort 2b) or, in subjects with
inadequate response post ASCT during initial treatment (Cohort 2c) Approximately 181 subjects
will be enrolled into one of two cohorts. Cohort 1 will enroll approximately 73 RRMM subjects
with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM
subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b
will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT
and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate
response to ASCT during their initial anti-myeloma therapy. The cohorts will start in
parallel and independently.
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
2. Subject has measurable disease, defined as:
• M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis
[uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
• Light chain MM without measurable disease in the serum or urine: Serum
immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin
kappa lambda free light chain ratio
3. Subjects with one of the following cohort specific requirements:
Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:
• Subject must have received at least 3 prior anti-myeloma treatment regimens.
Note: induction with or without hematopoietic stem cell transplant and with or
without maintenance therapy is considered a single regimen
• Subject must have undergone at least 2 consecutive cycles of treatment for each
regimen, unless PD was the best response to the regimen
• Subject must have received prior treatment with a proteasome inhibitor, an
immunomodulatory agent and an anti-CD38 antibody
• Subject has evidence of PD on or within 60 days of the most recent prior
treatment regimen
• Subject achieved a response (minimal response [MR] or better) to at least 1 prior
treatment regimen
Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:
• Subject must have received only 1 prior anti-myeloma treatment regimen. Note:
induction with or without hematopoietic stem cell transplant and with or without
maintenance therapy is considered a single regimen
• Subject must have the following HR factors:
•R-ISS stage III AND
• Early relapse defined as:
Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must
contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.
Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at
minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort
2c: Subject must have received minimum 3 cycles of induction therapy which must
contain at minimum, a proteasome inhibitor, an immunomodulatory agent and
dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD)
at first assessment between 70 to 110 days after last ASCT, with initial therapy
without consolidation and maintenance.
4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
5. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities
due to prior treatments, excluding alopecia and Grade 2 neuropathy
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. Subject used any investigational agents within 14 days of leukapheresis
2. Subject received any of the following within the last 14 days of leukapheresis:
1. Plasmapheresis
2. Major surgery (as defined by the investigator)
3. Radiation therapy other than local therapy for myeloma associated bone lesions
4. Use of any systemic anti-myeloma drug therapy
3. Subject with known central nervous system involvement with myeloma
4. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular
coagulation
5. History or presence of clinically relevant central nervous system (CNS) pathology
6. Subject with active or history of plasma cell leukemia, Waldenstrom's
macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis
7. Inadequate organ function Subject with a history of Class III or IV congestive heart
failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled
angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
prior to starting study treatment
8. Ongoing treatment with chronic immunosuppressants
9. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment
with any gene therapy-based therapeutic for cancer or investigational cellular therapy
for cancer or BCMA targeted therapy
10. Subject has received ASCT within 12 weeks prior to leukapheresis
11. Subject has history of primary immunodeficiency
12. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active
hepatitis B or active hepatitis A or C
13. Subject has uncontrolled systemic fungal, bacterial, viral or other infection
(including tuberculosis) despite appropriate antibiotics or other treatment
14. Subject with prior history of malignancies, other than MM, unless the subject has been
free of the disease for ≥ 5 years
15. Pregnant or lactating women
16. Subject with known hypersensitivity to any component of bb2121 product,
cyclophosphamide, fludarabine, and/or tocilizumab
Biological: bb2121
Multiple Myeloma
Multiple Myeloma, bb2121, Relapsed and Refractory Multiple Myeloma, High Risk Multiple Myeloma
Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL
This is a pilot study utilizing Marqibo® (vincristine sulfate liposome injection) combined
with dexamethasone, mitoxantrone and asparaginase (UK ALL R3) for relapsed acute
lymphoblastic leukemia (ALL).
Inclusion Criteria
Age
-Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.
Diagnosis
• Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or
mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with
or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
• Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL),
lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of
detectable disease (minimal residual disease level acceptable) with or without
extramedullary disease
Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for
patients ≤ 16 years of age.
Prior Therapy
• Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of
all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study,
unless otherwise specified. Subjects with disease related cytopenias will be eligible.
• Patients must have relapsed or refractory disease after attaining at least a first
remission. They may be in first to third relapse..
• Patients with Philadelphia chromosome t(9;22) positive disease must have received at
least two prior tyrosine kinase inhibitors.
• Patients who have experienced their relapse after a Hematopoietic stem cell
transplantation (HSCT) are eligible, provided they have no evidence of
graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time
of enrollment.
• Prior anthracycline lifetime cumulative exposure: Patients must have less than 320
mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline
chemotherapy.
1. Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior
cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2
for anthracycline calculation worksheet).
2. Cohorts B & C: There is no limit on prior anthracycline exposure.
• Hematopoietic growth factors: It must have been at least seven days since the
completion of therapy with granulocyte colony-stimulating factor (GCSF) or other
growth factors at the time of enrollment. It must have been at least 14 days since the
completion of therapy with pegfilgrastim (Neulasta®).
• Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic
agent. For agents that have known adverse events occurring beyond seven days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with the
study chair or vice chair.
• Monoclonal antibodies: At least three half-lives (or 30 days—whichever is longer) of
the antibody must have elapsed after the last dose of monoclonal antibody. (e.g.,
Rituximab = 66 days, Epratuzumab = 69 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy,
e.g. tumor vaccines, chimeric antigen receptor T-cells.
• Recent prior chemotherapy: At least 10 days after standard vincristine and the
completion of any type of chemotherapy induction regimen. At least 3 weeks after
radiation therapy. At least 30 days after the completion of any investigational
neoplastic agent is also required. An investigational agent is defined as any drug
that is not approved and licensed for sale by the FDA for institutions in the United
States, by Health Canada for institutions in Canada and by The Therapeutic Goods
Administration for institutions in Australia.
Exceptions:
• There is no time restriction in regard to prior intrathecal chemotherapy provided
there is complete recovery from any acute toxic effects of such; it is allowable to
enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or
triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose
disease relapse. The IT therapy given within 14 days of initiation of protocol
specified chemotherapy, may substitute for the day 1 IT in cohorts A and B
• Subjects with rapidly progressive disease may receive hydroxyurea until they begin
study therapy;
• Patients who relapse while on maintenance-type ALL therapy or are receiving
maintenance therapy for disease stabilization will not require a wash-out period
before entry into this study. However, there must be at least 10 days after any dose
of standard vincristine.
Renal and Hepatic Function
• Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit
of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times
normal, the patient must have a calculated creatinine clearance or radioisotope
glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour
creatinine clearance may also be used.
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x
ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN).
Cardiac Function
-Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by
echocardiogram, cardiac MRI or multigated acquisition scan (MUGA).
Reproductive Function
• Female patients must not be pregnant and those of childbearing potential must have a
negative urine or serum pregnancy test confirmed within one week prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this
study.
• Male and female patients of childbearing potential must agree to use an effective
method of contraception during the study.
Exclusion Criteria
Patients will be excluded if they have isolated testicular disease.
Patients will be excluded if they have previously received Marqibo®.
Patients will be excluded if they have a known allergy to any of the drugs used in the
study, with the exception that patients with an allergy to PEG-asparaginase who can receive
Erwinia asparaginase are eligible. Patients unable to receive any formulation of
asparaginase may only enroll on cohort C
Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial,
viral or other infection despite appropriate antibiotics or other treatment.
Patients who require azole antifungal agents will be excluded. Azoles must be discontinued
at least one week prior to the start of Marqibo®.
Patients will be excluded if there is a plan to administer non-protocol chemotherapy,
radiation therapy, another investigational agent or immunotherapy during the study period.
Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from
any cause will be excluded.
Patients will be excluded if they have, significant concurrent disease, illness,
psychiatric disorder or social issue that would compromise patient safety or adherence with
the protocol treatment or procedures or interfere with consent, study participation, follow
up, or interpretation of study results.Patients with Down syndrome will not be eligible for
enrollment on Cohort A
Patients with a known history of human immunodeficiency virus (HIV) will will be excluded
due to the increased risk of complications such as severe infection and unknown interaction
of Marqibo® with antiretroviral drugs.
Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B
surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above
the ULN per the institution normal ranges).
Drug: Marqibo
ALL, Childhood, Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Acute
Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma
This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib
and combination chemotherapy works in treating patients with newly diagnosed stage II-IV
anaplastic large cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called
brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive
cancer cells in targeted way and delivers vedotin to kill them. Crizotinib and methotrexate
may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either
by killing the cells, by stopping them from dividing, or by stopping them from spreading. It
is not yet known whether brentuximab vedotin and combination chemotherapy is more effective
than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma.
• Newly diagnosed patients with histologically proven ALCL (International Classification
of Diseases for Oncology [ICD-0] code: 9714/3)
• Disease must be cluster of differentiation (CD)30 positive
• Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local
institutional standards)
• Patients must have stage II, III, or IV disease
• Patients must have a life expectancy of >= 8 weeks
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x
upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT is
45 U/L (within 7 days prior to enrollment)
• If the lab abnormality is thought to be due to the lymphoma the patient is eligible
and dose adjustments should be made
• Shortening fraction of >= 27% by echocardiogram, or
• Ejection fraction of >= 50% by radionuclide angiogram
• Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at
rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry >
92% while breathing room air unless current dysfunction is due to the lymphoma in
which case the patient is eligible
Exclusion Criteria:
• Patients with central nervous system (CNS) disease are not eligible
• Patients with disease limited to the skin are not eligible, regardless of how
wide-spread
• Patients with stage I disease are not eligible
• Patients who have received any prior cytotoxic chemotherapy for the current diagnosis
of ALCL or any cancer diagnosed previously are not eligible
• Previous steroid treatment and/or radiation treatment is not allowed unless it is for
the emergent management of a mediastinal mass; emergent steroid treatment and/or
radiation treatment should stop once protocol therapy is initiated
• Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of
ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to administration
of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL
• Female patients who are pregnant are not eligible; pregnancy tests must be obtained in
girls who are post menarchal
• Lactating females are not eligible unless they have agreed not to breastfeed their
infants
• Sexually active patients of reproductive potential are not eligible unless they agree
to use an effective contraceptive method for the duration of treatment and for 3
months after stopping treatment
• Patients with Down syndrome are not eligible due to the amount of methotrexate and
potential for side effects
• Patients with an immunodeficiency that existed prior to diagnosis such as primary
immunodeficiency syndromes or organ transplant recipients are not eligible
• Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow
therapeutic indices: Patients chronically receiving medications known to be
metabolized by CYP3A4 and with narrow therapeutic indices including pimozide,
aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use
of these medications (if applicable) is allowed
• CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4
inhibitors within 7 days prior to study enrollment, including but not limited to
ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir,
nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit
juice are not eligible; the topical use of these medications (if applicable), e.g. 2%
ketoconazole cream, is allowed
• CYP3A4 inducers: patients chronically receiving drugs that are known potent CYP3A4
inducers within 12 days prior to study enrollment, including but not limited to
carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, ritonavir, and St.
John's wort are not eligible; the topical use of these medications (if applicable) is
allowed
• Patients that are known to be positive for human immunodeficiency virus (HIV) are not
eligible; note: inclusion of HIV positive patients will be considered at a later date
• Patients who weigh < 10 kg are not eligible
Anaplastic Large Cell Lymphoma, ALK-Positive, CD30-Positive Neoplastic Cells Present, Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma, Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma, Ann Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma
Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
This phase III trial studies response-based chemotherapy in treating newly diagnosed acute
myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome. Drugs
used in chemotherapy work in different ways to stop the growth of cancer cells, either by
killing the cells, by stopping them from dividing, or by stopping them from spreading.
Response-based chemotherapy separates patients into different risk groups and treats them
according to how they respond to the first course of treatment (Induction I). Response-based
treatment may be effective in treating acute myeloid leukemia or myelodysplastic syndrome in
younger patients with Down syndrome while reducing the side effects.
• Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism
(by karyotype or fluorescence in situ hybridization [FISH])
• Patient has one of the following:
• Patient has previously untreated de novo AML and meets the criteria for AML with
>= 20% bone marrow blasts as set out in the World Health Organization (WHO)
Myeloid Neoplasm classification
• Attempts to obtain bone marrow either by aspirate or biopsy must be made
unless clinically prohibitive; in cases where it is clinically prohibitive,
peripheral blood with an excess of 20% blasts and in which adequate flow
cytometric and cytogenetics/FISH testing is feasible can be substituted for
the marrow exam at diagnosis
• Patient has cytopenias and/or bone marrow blasts but does not meet the criteria
for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of < 20%
marrow blasts and meets the criteria for a diagnosis of myelodysplastic syndrome
(MDS)
• Patient has a history of transient myeloproliferative disorder (which may or may
not have required chemotherapy intervention), who:
• Are > 8 weeks since resolution of transient myeloproliferative disease (TMD) with
>= 5% blasts, OR
• Patients who have an increasing blast count (>= 5%) in serial bone marrow
aspirates performed at least 4 weeks apart
• Children who have previously received chemotherapy, radiation therapy or any
anti-leukemic therapy are not eligible for this protocol, with the exception of
cytarabine for the treatment of TMD
• There are no minimal organ function requirements for enrollment on this study
• Note: Previous cardiac repair with sufficient cardiac function is not an
exclusion criteria
• Each patient?s parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human subjects research must be met
Exclusion Criteria:
• Patients with promyelocytic leukemia (French-American-British [FAB] M3)
• Prior therapy
• Patients =< 30 days from the last dose of cytarabine used for treatment of TMD
Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer (CANVAS)
The overarching objective of the study is to determine the effectiveness of LMWH/ warfarin
vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The intervention
strategy is Direct Oral AntiCoagulants (DOAC) therapy with edoxaban, apixaban, rivaroxaban,
or dabigatran. The comparator is low molecular weight heparin (LMWH) alone or with warfarin.
The information gained will empower cancer patients and physicians to make more informed
choices about anticoagulation strategies to manage VTE.
• Diagnosis of advanced solid tumor cancer, lymphoma, or myeloma (no time restrictions
or limitations) -OR- diagnosis of early stage solid tumor cancer, lymphoma, or myeloma
<= 12 months prior to study enrollment
• Diagnosis of VTE <= 30 days prior to study enrollment for which potential benefits of
anticoagulation therapy to prevent recurrence of VTE are felt by the treating
physician to exceed the potential harms
• Any anticoagulation drug/strategy may be used to treat the index VTE; protocol
treatment will begin <= 30days after the index VTE diagnosis date
• Treating physician intends to put participant on anticoagulation therapy for at least
three months.
• Age >= 18 years
• Platelet count is >= 50,000/mm^3 (<= 7 days prior to enrollment)
• CrCl (Creatinine Clearance) is >= 15 ml/min (<= 7 days prior to enrollment)
Exclusion Criteria:
• Diagnosis of acute leukemia
• Has ever received or is scheduled to receive an Allogeneic Hematopoietic Stem Cell
Transplantation (alloHSCT)
• Patients who have ever received an Autologous Hematopoietic Stem Cell
Transplantation (autoHSCT) ARE eligible.
• Patients who are scheduled to receive an Autologous Hematopoietic Stem Cell
Transplantation (autoHSCT) are NOT eligible
• Ongoing, clinically significant bleeding (CTCAE grade 3 or 4)
• Ongoing therapy with a P-gp inhibitor (e.g., nelfinavir, indinavir, or
saquinavir-protease inhibitors for HIV) as these drugs interact with the factor Xa
inhibitors
• Therapy with any azole antifungals (e.g., itraconazole, ketaconazole, voriconazole) at
the time of enrollment
Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients (BIANCA)
The purpose of the study is to assess the efficacy and safety of tisagenlecleucel in children
and adolescents with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). For
pediatric patients who have r/r B-NHL, survival rates are dismal, only ~20-50% subjects are
alive at 2 years with overall response rate (ORR) of 20-30% after conventional salvage
chemotherapy.
• Histologically confirmed pediatric mature B-cell non-Hodgkin lymphoma (B-cell NHL)
including the following subtypes; Burkitt lymphoma (BL), diffuse large B-cell lymphoma
(DLBCL), primary mediastinal B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), and
follicular lymphoma (FL) Note: Patients with bone marrow involvement of >25% lymphoma
cells by bone marrow biopsy/aspirate evaluation, will be excluded. Patients with
B-cell NHL associated with Nijmegen breakage syndrome will be allowed.
• Patients <18 years of age and weighing at least 6 kg at the time of screening
• Patients who have relapsed after one or more prior therapies (can include allogeneic
and autologous hematopoietic stem cell transplant) or are primary refractory (have not
achieved a CR or PR after the first line of therapy)
• Measurable disease by radiological criteria in all patients at the time of screening.
• Karnofsky (age ≥16 years) or Lansky (age <16 years) performance status ≥60.
• Adequate bone marrow reserve without transfusions (transfusion >2 weeks prior to
laboratory assessment is allowed) defined as:
1. Absolute neutrophil count (ANC) >1000/mm3
2. Absolute lymphocyte count (ALC) >300/mm3
3. absolute number of CD3+ T cells >150/mm3
4. Platelets ≥50000//mm3
5. Hemoglobin ≥8.0 g/dl
• Adequate organ function defined as:
1. a serum creatinine (sCR) based on gender/age as follows: Maximum Serum Creatinine
(mg/dL) Age Male Female
1 to <2 years 0.6 0.6 2 to <6 years 0.8 0.8 6 to <10 years 1.0 1.0 10 to <13
years 1.2 1.2 13 to <16 years 1.5 1.4
≥16 years 1.7 1.4
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the
upper limit of normal (ULN) for age
3. Total bilirubin <2 mg/dL (for Gilbert's Syndrome patients total bilirubin <4
mg/dL)
4. Adequate pulmonary function
i. Oxygen saturation of >91% on room air ii. No or mild dyspnea (≤Grade 1)
• Must have a leukapheresis material of non-mobilized cells accepted for manufacturing.
Exclusion Criteria:
• Prior gene therapy or engineered T cell therapy.
• Prior treatment with any anti-CD19 therapy.
• Allogeneic hematopoietic stem cell transplant (HSCT) <3 months prior to screening and
≤4 months prior to infusion.
• Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)
in patients who received prior allogeneic HSCT.
• Prior diagnosis of malignancy other than study indication, and not disease free for 5
years.
• Active, uncontrolled infection despite treatment at screening.
• Presence of active or prior hepatitis B or C as indicated by serology.
• Human Immunodeficiency Virus (HIV) positive test.
• Active neurological autoimmune or inflammatory disorders not related to B cell NHL
(eg: Guillain-Barre syndrome, Amyotrophic Lateral Sclerosis)
• Active central nervous system (CNS) involvement by malignancy.
• Patients with B-cell NHL in the context of post-transplant lymphoproliferative
disorders (PTLD) associated lymphomas.
Other protocol-defined inclusion/exclusion criteria may apply.
Biological: Tisagenlecleucel
Non-hodgkin Lymphoma
Tisagenlecleucel, relapsed/refractory B-cell non-Hodgkin lymphoma, pediatric patients, Burkitt's lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), follicular lymphoma (FL), leukapheresis, lymphodepleting chemotherapy (LD), NHL
Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd Salvage
Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with
AML relapsed/refractory after 2 or 3 prior induction regimens:
Experimental arm: DFP-10917 14-day continuous intravenous (IV) infusion at a dose of 6
mg/m²/day followed by a 14-day resting period per 28-day cycles.
Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine) or Intensive
Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's
prior induction treatment.
1. Histologically or pathologically confirmed diagnosis of AML based on World Health
Organization (WHO) classification that has relapsed after, or is refractory to, two or
three prior induction regimens that may have included intensive chemotherapy (e.g.,
"7+3" cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or
decitabine) , or targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal antibody).
(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts
in peripheral blood 90 days to 24 months after first CR or CR without complete
platelet recovery (CRp). Refractory AML is defined as persistent disease ≥28 days
after initiation of intensive induction therapy (up to two induction cycles) or
relapse <90 days after first CR or CRp. Refractory disease for patients undergoing
hypomethylating agent induction is defined as lack of remission following at least 2
cycles of epigenetic therapy without reduction in bone marrow blast status.)
2. Aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
4. Adequate clinical laboratory values (i.e., plasma creatinine < 2.5 x upper limit of
normal (ULN) for the institution, bilirubin < 2.5 x ULN, alanine transaminase (ALT)
and aspartate transaminase (AST) ≤ 2.5 x ULN).
5. Absence of active central nervous system (CNS) involvement by leukemia. Patients with
previously diagnosed CNS leukemia are eligible if the CNS leukemia is under control
and intrathecal treatment may continue throughout the study.
6. Absence of uncontrolled intercurrent illnesses, including uncontrolled infections,
cardiac conditions, or other organ dysfunctions.
7. Signed informed consent prior to the start of any study specific procedures.
8. Women of child-bearing potential must have a negative serum or urine pregnancy test.
9. Male and female patients must agree to use acceptable contraceptive methods for the
duration of the study and for at least one month after the last drug administration.
Exclusion Criteria:
1. The interval from prior treatment to time of study drug administration is < 2 weeks
for cytotoxic agents or < 5 half-lives for noncytotoxic agents. Exceptions: Use of
hydroxyurea is allowed before the start of study and is to be discontinued prior to
randomization. Hydroxyurea may be administered before study start and up to the time
of study randomization. At the investigator's discretion, for patients with
significant leukocytosis during the early treatment cycles, hydroxyurea may be
administered. The hydroxyurea should be discontinued as soon as clinically
appropriate.
2. Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.
3. Cardiac (left ventricular ejection fraction ≤40%) function.
4. White blood cell (WBC) >15,000/uL.
5. For patients with prior hematopoietic stem cell transplant (HSCT):
1. Less than 3 months since HSCT
2. Acute Graft versus Host Disease (GvHD) >Grade 1
3. Chronic GvHD >Grade 1
6. Any concomitant condition that in the opinion of the investigator could compromise the
objectives of this study and the patient's compliance.
7. A pregnant or lactating woman.
8. Current malignancies of another type. Exceptions: Patients may participate if they
have previously treated and currently controlled prostate cancer, or adequately
treated in situ cervical cancer or basal cell skin cancer, or other malignancies with
no evidence of disease for 2 years or more.
9. Patient has acute promyelocytic leukemia (APL).
10. Patients with known HIV, HBV or HCV infection (note: testing for these infections is
not required).
11. Documented or known clinically significant bleeding disorder.
Pharmacodynamic & Safety of Patiromer in Children & Adolescents (2-<18 Yrs) With Chronic Kidney Disease and Hyperkalemia (EMERALD)
The purpose of this study is to evaluate the change in serum (blood) potassium levels from
start of treatment to Day 14, when patiromer is administered at different doses, once daily,
in children 2 - < 18 years of age with chronic kidney disease (CKD) and hyperkalemia (too
much potassium in the blood). Another purpose of the study is to evaluate the safety and
tolerability of patiromer in children 2 - < 18 years of age with CKD and hyperkalemia.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Mouin Seikaly
16504
All
2 Years to 17 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03087058
STU 022017-042
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Written assent (when applicable) and written informed consent by a legally authorized
representative provided prior to participation in the study
• Age 2 •<18 years old
• CKD defined by eGFR <60 mL/min/1.73m2 including renal transplant, peritoneal dialysis
• Two potassium measurements of 5.1 to < 6.5 mEq/L performed on separate days
• In the opinion of the study doctor, is expected to require treatment for hyperkalemia
for at least 6 months
• If taking any renin-angiotensin-aldosterone system inhibitors (RAASi) beta blockers or
diuretic medications, must be on a stable dose for at least 28 days prior to Screening
• Negative pregnancy test in females of child-bearing potential
Exclusion Criteria:
• False elevation in blood potassium (pseudohyperkalemia) due to hemolysis (breaking of
blood cells) or abnormally high counts of blood cells at Screening
• Evidence of potassium-related electrocardiogram (ECG) changes at Screening
• Any of the following kidney conditions: hemodialysis, renal artery stenosis, and acute
kidney injury or a history of acute renal insufficiency in the past 3 months
• Severe disorder of stomach or intestines including surgery
• Increased liver enzymes (ALT, AST > 3 times upper limit of normal) at Screening
• Active cancer, currently on cancer treatment or history of cancer in the past 2 years
(except for non-melanoma skin cancer)
• Have had a heart or liver transplant, or anticipated need for transplant during the
study treatment period including a scheduled kidney transplant. (Note: patients
currently on a kidney transplant wait list are not excluded unless there is an
identified donor).
• Alcohol abuse or substance use disorder within 1 year of Screening
• Subjects currently being treated with or having taken any one of the following
medications (includes resins) in the 7 days prior to Screening: sodium or calcium
polystyrene sulfonate, drospirenone
• Use of certain medications that can affect blood potassium levels if doses have not
been stable for at least 14 days prior to Screening or if doses are anticipated to
change during the 14-day PD / Dose Finding Phase
• Use of investigational product within 30 days of screening or within 5 half-lives,
whichever is longer
• Known hypersensitivity to patiromer or its components
• In the opinion of the Investigator, any medical condition, uncontrolled systemic
disease, or serious intercurrent illness that would significantly decrease study
compliance or jeopardize the safety of the subject or potentially affect the quality
of the data
Drug: Patiromer, Drug: Patiromer, Drug: Patiromer
Hyperkalemia
Treatment of Hyperkalemia, Hyperkalemia, Potassium, Chronic Kidney Disease
Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA (INSPIRE)
The study's primary objective [in a population of patients with MDS after failure of
treatment with azacitidine (AZA) or decitabine (DAC)], is to compare the overall survival
(OS) of patients in the rigosertib group vs the Physician's Choice group, in all patients and
in a subgroup of patients with IPSS-R very high risk.
• MDS classified as follows:
• RAEB-1 per World Health Organization (WHO) MDS criteria (5% to <10% BM blasts)
• RAEB-2 per WHO MDS criteria (10% to <20% BM blasts)
• RAEB-t per French-American-British (FAB) classification (20% to 30% BM blasts)
• At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin
[Hgb] < 10 g/dL)
• Progression (according to 2006 IWG criteria) at any time after initiation of AZA or
DAC treatment or Failure to achieve complete or partial response or hematological
improvement (HI) (according to 2006 IWG) after at least six 4-week cycles of AZA or
either four 4-week or four 6-week cycles of DAC administered or Relapse after initial
complete or partial response or HI (according to 2006 IWG criteria)
• Duration of prior HMA therapy ≤ 9 months and/or total ≤ 9 cycles of prior HMA therapy
in ≤ 12 months
• Last dose of AZA or DAC within 6 months before the planned date of randomization;
however, must be off these treatments for ≥ 4 weeks before randomization
• Has failed to respond to, relapsed following, not eligible for, or opted not to
participate in allogeneic stem cell transplantation
• Off all treatments for MDS (including AZA and DAC) for ≥ 4 weeks before randomization;
growth factors (G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed
before and during the study as clinically indicated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Willing to adhere to protocol prohibitions and restrictions
• Patient must sign informed consent form to indicate patient's understanding study's
purpose and procedures and willingness to participate. Should patient be incapable of
giving consent, the patient's legally authorized representative (as defined by local
regulation) must give consent. However, should patient, in any manner, choose not to
participate this takes precedence and will be respected.
• Patients with 5q- syndrome should have failed to respond to or progressed on treatment
with lenalidomide, where available and indicated
Exclusion Criteria:
• Previous participation in a clinical study of IV or oral rigosertib; patients who
failed screening for other rigosertib studies may be screened for participation
• Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside
plus 2-3 days of an anthracycline, or high-dose cytarabine
• Suitable candidate to receive allogeneic stem cell transplantation; patient is
eligible for study if a suitable candidate refuses to undergo an allogeneic stem cell
transplant or a suitable donor cannot be found
• Any active malignancy within the past year, except basal cell or squamous cell skin
cancer or carcinoma in situ that is unlikely to progress in two years
• Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure or unstable angina pectoris
• Active infection not adequately responding to appropriate therapy
• Total bilirubin ≥1.5 mg/dL not related to hemolysis or Gilbert's disease
• Alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal
(ULN)
• Serum creatinine ≥2.0 mg/dL or eGFR (estimated Glomerular Filtration Rate) < 40
mL/min.
• Known active HIV, hepatitis B or hepatitis C, where active is defined as follows:
• HIV or hepatitis C •presence of viral load
• Hepatitis B •antigen positive
• Uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L)
• Female patients of child-bearing potential and male patients with sexual partners of
child-bearing potential who are unwilling to follow strict contraception requirements
before entry and throughout the study, up to and including the 30-day non-treatment
follow-up period. Examples of acceptable contraception methods include:
• estrogen-gestagen based contraceptives associated with inhibition of ovulation
(oral, intravaginal, transdermal),
• gestagen-only based contraceptives associated with inhibition of ovulation (oral,
injectable, implantable),
• intra-uterine devices (IUDs),
• intra-uterine hormone-releasing systems (IUSs),
• bilateral tubal occlusion
• vasectomized partner
• sexual abstinence in accordance with an individual's lifestyle
• Female patients of child-bearing potential (pre-menopausal and not surgically
sterilized) who are breast-feeding or have a positive blood beta-human chorionic
gonadotropin pregnancy test at Screening
• Major surgery without full recovery or within 3 weeks before planned randomization;
• Uncontrolled hypertension
• New onset seizures (within 3 months before planned randomization) or poorly controlled
seizures
• Any other concurrent investigational agent or chemotherapy, radiotherapy,
immunotherapy, or corticosteroids (prednisone up to 20 mg/day or its equivalent is
permitted for chronic conditions)
• Treatment with cytarabine at any dose, lenalidomide, or any other therapy targeted to
the treatment of MDS (other than growth factors and other supportive care measures)
within 4 weeks of planned randomization
• Investigational therapy within 4 weeks of planned randomization
• Psychiatric illness or social situation that would limit the patient's ability to
tolerate and/or comply with study requirements.
• Patient previously diagnosed with AML (defined as a bone marrow or peripheral blood
blast percentage of >30%).
Drug: rigosertib, Drug: Any approved or standard-of-care therapy, Drug: best supportive care (BSC), Drug: best supportive care (BSC)
Myelodysplastic Syndrome, Refractory Anemia With Excess Blasts, MDS, RAEB
A Trial of Temsirolimus With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma
This is a phase I study of temsirolimus (Torisel) combined with dexamethasone,
cyclophosphamide and etoposide in patients with relapsed acute lymphoblastic leukemia (ALL),
lymphoblastic lymphoma (LL) or peripheral T-cell lymphoma (PTL).
INCLUSION CRITERIA
-Patients must be greater than or equal to 12 months and ≤ 21 years of age at the time of
study enrollment.
Patients must have one of the following:
Leukemia
• Patients must have relapsed or refractory acute lymphoblastic leukemia (ALL) with
greater than or equal to 25% blasts in the bone marrow (M3). OR
• Patients may have an M2 marrow (greater than or equal to 5% to < 25% blasts) with an
extramedullary site of relapse; including CNS 2 and CNS 3.
• Refractory disease defined as no more than 1 prior failed salvage attempt following
the current relapse, or no more than 2 additional treatment cycles after initial
induction failure in newly diagnosed patients.
Lymphoma
• Patient must have relapsed or refractory lymphoblastic lymphoma or peripheral T-cell
lymphoma.
• Patient must have histologic verification of disease at original diagnosis.
• Patient must have evaluable or measurable disease documented by clinical or
radiographic criteria or bone marrow disease present at study entry.
• Patients may have CNS 2 or 3 disease, if other sites of involvement.
Karnofsky greater than or equal to 50% for patients > 16 years of age and Lansky greater
than or equal to 50 for patients ≤ 16 years of age.
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer
chemotherapy.
Patients must have had 2 or more prior therapeutic attempts defined as:
• Relapse after going into remission from re-induction for the first or subsequent
relapse (ie: 2nd , 3rd, 4th…relapse), or
• Patients with lymphoma may have refractory disease after first or greater relapse and
a single re-induction attempt.
Patients with leukemia or lymphoma who relapse while receiving maintenance chemotherapy
will not be required to have a waiting period before enrollment onto this study.
At least 14 days must have elapsed after the completion of cytotoxic therapy, with the
exception of hydroxyurea.
Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth
factor (e.g. Neulasta) or 7 days for short-acting growth factor.
Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent.
For agents that have known adverse events occurring beyond 7 days after administration,
this period must be extended beyond the time during which adverse events are known to
occur. The duration of this interval must be discussed with the study chair
Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g.
tumor vaccines. or chimeric antigen receptor T cell (CART) therapy.
Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the
last dose of a monoclonal antibody. (ie: Rituximab = 66 days, Epratuzumab = 69 days).
Patients must have been off blinatumomab infusion for at least 7 days and all drug-related
toxicity must have resolved to grade 2 or lower as outlined in the inclusion and exclusion
criteria
XRT: At least 14 days after local palliative XRT (small port); At least 84 days must have
elapsed if prior TBI, craniospinal XRT or if greater than or equal to 50% radiation of
pelvis; At least 42 days must have elapsed if other substantial marrow radiation.
Stem Cell Infusion: No evidence of active graft vs. host disease and at least 84 days must
have elapsed after transplant or stem cell infusion.
Study specific limitations on prior therapy: Patient may not have received therapy with an
mTOR inhibitor.
Adequate Bone Marrow Function Defined as: Blood counts are not required to be normal prior
to enrollment on trial. However, platelet count must be greater than or equal to
20,000/mm3 to initiate therapy (may receive platelet transfusions). Patients should not be
known to be refractory to red blood cell or platelet transfusions.
Adequate Renal Function Defined as:
• Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2 or
• Normal serum creatinine based on age and gender.
Adequate Liver Function Defined as:
• Total bilirubin (sum of conjugated + unconjugated) must be less than or equal to 1.5
x normal per institutional normal values for age.
• SGPT (ALT) and SGOT (AST) must be less than 3 x institutional upper limit of normal
(Grade 1 or less per CTCAE 4).
--GGT must be less than 2.5 x institutional upper limit of normal (Grade 1 or less
per CTCAE 4).
• Serum albumin greater than or equal to 2 g/dL.
• The hepatic requirements may be waived for patients with elevations clearly due to
leukemic infiltration after consultation with the Study Chair or Vice Chair.
• Fasting or non-fasting serum triglyceride level ≤ 300 mg/dL and serum cholesterol
level ≤ 300 mg/dL.
Adequate Cardiac Function Defined As:
• Shortening fraction of ≥ 27% by echocardiogram, or
• Ejection fraction of ≥ 50% by gated radionuclide study.
Adequate Pulmonary Function Defined as:
• Pulse oximetry > 94% on room air (> 90% if at high altitude)
• No evidence of dyspnea at rest and no exercise intolerance.
• Baseline chest x-ray with no evidence of active infectious disease or pneumonitis.
Reproductive Function
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test confirmed prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this
study.
• Male and female patients of child-bearing potential must agree to use an effective
method of contraception approved by the investigator during the study.
• Random or fasting glucose within the upper limits of normal for age. If the initial
blood glucose is non-fasting and above normal limits a fasting glucose can be
obtained and must be within the upper limits of normal for age.
EXCLUSION CRITERIA
• Corticosteroids: Patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment are not
eligible.
• Investigational Drugs: Patients who are currently receiving another investigational
drug are not eligible. The definition of "investigational" for use in this protocol
means any drug that is not licensed by the FDA, Health Canada or the Therapeutic
Goods Administration to be sold in the countries they govern. (United States, Canada
and Australia)
• Anti-cancer Agents: Patients who are currently receiving or may receive while on
therapy, other anti-cancer agents, radiation therapy or immunotherapy are not
eligible [except leukemia patients receiving hydroxyurea, which may be continued
until 24 hours prior to start of protocol therapy]. Intrathecal chemotherapy (at the
discretion of the primary oncologist) may be given up to one week prior to the
initiation of study therapy.
• Anti-GVHD or agents to prevent organ rejection post-transplant: Patients who are
receiving cyclosporine, tacrolimus or other agents to prevent either
graft-versus-host disease post bone marrow transplant or organ rejection post
transplant are not eligible for this trial. At least 3 half-lives must have elapsed
after the last dose of GVHD meds.
• Anticoagulants: Patients who are currently receiving therapeutic anticoagulants
(including aspirin, low molecular weight heparin, and others) are not eligible. At
least 3 half-lives must have elapsed after the last dose of anticoagulants.
• Angiotensin-converting enzyme (ACE) inhibitors: Patients who are currently receiving
ACE inhibitors are not eligible due to the development of angioneurotic edema-type
reactions in some subjects who received concurrent treatment with temsirolimus + ACE
inhibitors. At least 3 half-lives must have elapsed after the last dose of ACE
inhibitors.
• Enzyme inducing Anti-convulsants: Patients who are currently receiving enzyme
inducing anticonvulsants (ie phenytoin, phenobarbitol, or carbamazepine) are not
eligible. Stabilizing on a non-hepatic inducing metabolizing anti-convulsant (ie:
gabapentin or levetiracetam) prior to study entry is acceptable. At least 3
half-lives must have elapsed after the last dose of enzyme inducing anti-coagulants.
• Patients receiving treatment with azoles such as fluconazole or voriconazole which
are potent inhibitors of temsirolimus metabolism. At least 3 half-lives must have
elapsed after the last dose of azoles.
Infection Criteria
Patients are excluded if they have:
• Positive blood culture within 48 hours of study enrollment;
• Fever above 38.2 within 48 hours of study enrollment with clinical signs of
infection. Fever that is determined to be due to tumor burden is allowed if patients
have documented negative blood cultures for at least 48 hours prior to enrollment and
no concurrent signs or symptoms of active infection or hemodynamic instability.
• A positive fungal culture within 30 days.
• Active fungal, viral, bacterial, or protozoal infection requiring IV treatment.
Chronic prophylaxis therapy to prevent infections is allowed.
Patients with Down syndrome and Fanconi Anemia are excluded.
Patients will be excluded if they have significant concurrent disease, illness,
psychiatric disorder or social issue that would compromise patient safety or compliance
with protocol treatment or required observations, interfere with consent, study
participation, follow up, or interpretation of study results.
Patients with known optic nerve and/or retinal involvement (because it may not be possible
to safely delay irradiation) are not eligible. Patients presenting with visual
disturbances by history or physical exam should have an ophthalmological exam and, if
indicated, an MRI to determine optic nerve or retinal involvement.
A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
The purpose of this study is to confirm that the pharmacokinetics of ibrutinib in pediatric
participants is consistent with that in adults (part 1) and to assess efficacy (event-free
survival [EFS]) of ibrutinib in combination with rituximab, ifosfamide, carboplatin, and
etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, and idarubicin (RVICI)
background therapy compared to RICE or RVICI background therapy alone (part 2).
• Participants with 1 to less than (<) 18 years of age (Part 1 only), or 1 to 30 years
of age, inclusive, if initial diagnosis of mature B-cell non-Hodgkin lymphoma (NHL)
occurred at <18 years of age (Part 2 only)
• Participants must be in first recurrence or have disease that is primarily refractory
to conventional therapy
• Participants must have at least 1 of the following: 1 site of measurable disease
greater than (>) 1 centimeter (cm) in the longest diameter and >1 cm in the shortest
diameter by radiological imaging; bone marrow involvement; cerebrospinal fluid with
blasts present
• Participants with lansky-Karnofsky score of greater than or equal to (>=) 50
• Adolescent women/young women of childbearing potential must have a negative highly
sensitive serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test
at Screening before enrollment/randomization. Adolescent/young women who are pregnant
or breastfeeding are ineligible for this study
Exclusion Criteria:
• Participants with ongoing anticoagulation treatment with warfarin or equivalent
vitamin K antagonists (example phenprocoumon), or ongoing treatment with agents known
to be strong CYP3A4/5 inhibitors, or has taken any disallowed therapies as noted in
Section 8.2, Prohibited Medications, before the planned first dose of study drug
• Participants with inherited or acquired bleeding disorders
• Participants with clinically significant arrhythmias, complex congenital heart
disease, or left ventricular ejection fraction (LVEF) <50 percent (%) or shortening
fraction (SF) <=28%
• Participants with known history of human immunodeficiency virus (HIV) or active
Hepatitis B or C virus
• Participants with any condition that could interfere with the absorption or metabolism
of ibrutinib including malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small bowel
• Participants with known allergies, hypersensitivity, or intolerance to ibrutinib or
its excipients (refer to Investigator's Brochure)
• A diagnosis of post-transplant lymphoproliferative disease (PTLD)
• Participants who are within 6 months of an allogeneic bone marrow transplant
• Participants who have had prior exposure to ibrutinib
A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary
efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric
participants with relapsed/refractory acute lymphoblastic leukemia (ALL) or
relapsed/refractory lymphoblastic lymphoma. A safety expansion cohort of approximately 20
patients may be enrolled in addition to the 50 participants in dose-escalation cohort.
• Must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or
refractory lymphoblastic lymphoma (LL). Refractory is defined as persistent disease
after at least 2 courses of chemotherapy.
• Participants with ALL with Philadelphia chromosome or with an ABL class
targetable fusion are eligible.
• Participants with LL must have radiographic evidence of disease
• Participants <= 18 years of age who do not have a standard of care treatment option
available.
• Must weigh greater than or equal to 20 kg.
• Must be able to swallow pills.
• Must have adequate hepatic and kidney function.
• Must have adequate performance status:
• Participants less than or equal to 16 years of age: Lansky greater than or equal
to 50
• Participants greater than 16 years of age: Karnofsky greater than or equal to 50
or Eastern Cooperative Oncology Group (ECOG) less than 3.
Exclusion Criteria:
• Participant has central nervous system (CNS) disease with cranial involvement that
requires radiation.
• Participants who are less than 100 days post-transplant, or greater than 100 days
post-transplant with active graft versus host disease (GVHD), or are still continuing
post-transplant immunosuppressant therapy within 7 days prior to the first dose of
study drug.
• Participants who have received any of the following prior to the first dose of study
drug:
• Inotuzumab within 30 days (if participant received inotuzumab > 30 days prior to
Day 1, must have ALT, AST and bilirubin < ULN).
• A biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent within
30 days
• CAR-T infusion or other cellular therapy within 30 days
• Any anti-cancer therapy including blinatumomab, chemotherapy, radiation therapy
targeted small molecule agents or investigational agents within 14 days, or 5
half-lives, whichever is shorter
• Exception: Philadelphia Chromosome (Ph)+ ALL subjects on TKIs at Screening
may enroll and remain on Tyrosine Kinase Inhibitor (TKI) therapy to control
disease. Participants on venetoclax at screening may enroll and remain on
venetoclax.
• Steroid therapy for anti-neoplastic intent within 5 days
• Hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose)
• A strong or moderate CYP3A inhibitor or inducer within 7 days
• Aspirin within 7 days, or 5 half-lives, whichever is longer
• An excluded antiplatelet/anticoagulant drug or a herbal supplement that affects
platelet function within 7 days, or 5 half-lives, whichever is longer
• Participants with malabsorption syndrome or any other condition that precludes enteral
administration.
Physical Activity in Children at Risk of Post-thrombotic Syndrome (PACT) (PACT)
'The PACT trial' is randomized pilot trial to demonstrate the feasibility and potential
effectiveness of a personal "fitness tracker" to improve adherence to an activity regimen
following an initial acute DVT in children.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Ayesha Zia
149180
All
7 Years to 21 Years old
N/A
This study is NOT accepting healthy volunteers
NCT03075761
STU 022016-057
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Hide eligibility criteria
Inclusion Criteria:
• A radiologically confirmed, acute, proximal first lower extremity DVT
• 4 to 8 weeks after starting anticoagulation
• Out-patient ambulatory status
Exclusion Criteria:
• Contraindication to increasing activity such as patients with juvenile arthritis, poor
balance, congestive heart failure, etc.
Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation
This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single
agent or in combination with azacitidine or cytarabine. The Phase 1 stage of the study is
split into 2 distinct parts: a dose escalation part, which will utilize an open-label design
of FT-2102 (single agent) and FT-2102 + azacitidine (combination agent) administered via one
or more intermittent dosing schedules followed by a dose expansion part. The dose expansion
part will enroll patients in up to 5 expansion cohorts, exploring single-agent FT-2102
activity as well as combination activity with azacitidine or cytarabine. Following the
completion of the relevant Phase 1 cohorts, Phase 2 will begin enrollment. Patients will be
enrolled across 8 different cohorts, examining the effect of FT-2102 (as a single agent) and
FT-2102 + azacitidine (combination) on various AML/MDS disease states.
• Pathologically proven acute myeloid leukemia (AML) (except acute promyelocytic
leukemia [APL] with the t(15;17) translocation) or intermediate, high-risk, or very
high risk Myelodysplastic Syndrome (MDS) as defined by the World Health Organization
(WHO) criteria or Revised International Prognostic Scoring System (IPSS-R) which is
relapsed or refractory (R/R) to standard therapy and/or for which standard therapy is
contraindicated or which has not adequately responded to standard therapy.
• Patients must have documented IDH1-R132 gene-mutated disease as evaluated by the site
• Good performance status
• Good kidney and liver function
Exclusion Criteria:
• Patients with symptomatic central nervous system (CNS) metastases or other tumor
location (such as spinal cord compression, other compressive mass, uncontrolled
painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention,
palliative care, surgery or radiation therapy
• Congestive heart failure (New York Heart Association Class III or IV) or unstable
angina pectoris. Previous history of myocardial infarction within 1 year prior to
study entry, uncontrolled hypertension or uncontrolled arrhythmias
• Pulmonary disease (e.g. COPD, asthma, etc) that is not controlled (moderate to severe
symptoms) with current medication
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy
Stem Cell Transplantation With NiCord® (Omidubicel) vs Standard Umbilical Cord Blood in Patients With Leukemia, Lymphoma, and Myelodysplastic Syndrome (MDS)
This study is an open-label, controlled, multicenter, international, Phase III, randomized
study of transplantation of NiCord® versus transplantation of one or two unmanipulated,
unrelated cord blood units in patients with acute lymphoblastic leukemia or acute myeloid
leukemia, myelodysplastic syndrome, chronic myeloid leukemia or lymphoma, all with required
disease features rendering them eligible for allogeneic transplantation.
• Applicable disease criteria
• Patients must have one or two partially HLA-matched CBUs
• Back-up stem cell source
• Adequate Karnofsky/Lansky Performance score
• Sufficient physiological reserves
• Signed written informed consent
Exclusion Criteria:
• HLA-matched donor able to donate
• Prior allogeneic HSCT
• Other active malignancy
• Active or uncontrolled infection
• Active/symptoms of central nervous system (CNS) disease
• Pregnancy or lactation
Drug: NiCord® (omidubicel), Other: Cord Blood Unit
Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients (CASSIOPEIA)
This is a single arm, open-label, multi-center, phase II study to determine the efficacy and
safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who
received first-line treatment and are EOC MRD positive. The study will have the following
sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After
tisagenlecleucel infusion, efficacy will be assessed at Day 29, then every 3 months for the
first year, every 6 months for the second year, then yearly until the end of the study.
Safety will be assessed throughout the study. The study is expected to end in approximately 8
years after first patient first treatment (FPFT). A post-study long term follow-up for
lentiviral vector safety will continue under a separate protocol per health authority
guidelines.
1. CD19 expressing B-cell Acute Lymphoblastic Leukemia
2. De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC
bone marrow MRD will be collected prior to screening and will be assessed by
multi-parameter flow cytometry using central laboratory analysis.
3. Age 1 to 25 years at the time of screening
4. Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
5. Adequate organ function during the screening period:
A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times
ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total
bilirubin < 4 mg/dL)
E. Adequate pulmonary function defined as:
• no or mild dyspnea (≤ Grade 1)
• oxygen saturation of > 90% on room air F. Adequate cardiac function defined as
LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram
or MUGA within 6 weeks of screening
6. Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks
of standard chemotherapy for first-line B-ALL, defined as 4-drug induction, augmented
Berlin-Frankfurt-Münster (BFM) consolidation, and interim maintenance with high-dose
methotrexate.
Exclusion Criteria:
1. M3 marrow at the completion of 1st line induction therapy
2. M2 or M3 marrow or persistent extramedullary disease at the completion of first-line
consolidation therapy. Patients with previous CNS disease are eligible if there is no
active CNS involvement of leukemia at the time of enrollment.
3. Philadelphia chromosome positive ALL
4. Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence
of a hypodiploid clone
5. Prior tyrosine kinase inhibitor therapy
6. Subjects with concomitant genetic syndromes associated with bone marrow failure
states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or
any other known bone marrow failure syndrome. Subjects with Down syndrome will not be
excluded.
7. Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia
with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3
morphology and /or a MYC translocation)
8. Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or
engineered T cell therapy
Other protocol-defined inclusion/exclusion may apply.
Biological: CTL019
B-cell Acute Lymphoblastic Leukemia
CTL019, Kymriah, B-Cell Acute Lymphoblastic Leukemia, ALL, tisagenlecleucel, HR B-ALL EOC MRD, Minimal Residual Disease (MRD), Positive at the End of Consolidation (EOC)
PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
This is a phase 1/2 study of a drug called Ixazomib in combination with cytotoxic
chemotherapy consisting of Vincristine, Dexamethasone, Asparaginase, and Doxorubicin (VXLD).
• Age Patients must be ≤21 years of age at the time of enrollment.
1. Phase 1 •Initial enrollment will be restricted to patients < 18 years of age
until 9 such patients are enrolled
2. Phase 2 •Initial enrollment will be restricted to patients < 18 years of age
until 6 such patients are enrolled
• Diagnosis Patients must have a diagnosis of relapsed/refractory ALL or LLy with or
without extramedullary disease (including CNS2 and CNS3). Patient with mixed phenotype
ALL or mature B (Burkitt-like) leukemia are not eligible.
1. Patients with ALL must have ≥ 5% blasts by morphology.
2. Patients with LLy must have measurable disease documented by clinical, radiologic
or histologic criteria
• Performance Level Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for
patients ≤ 16 years of age.
• Prior Therapy A. Prior therapeutic attempts
• Phase 1 •Any patients with relapsed/refractory ALL or LLy
• Phase 2
1. B-cell ALL/LLy: all patients must have failed two or more therapeutic
attempts.
2. T-cell ALL/LLy: all patients must have failed one or more therapeutic
attempts. B. Recent prior chemotherapy Patients must have fully recovered
from the acute toxic effects of all prior chemotherapy, immunotherapy, or
radiotherapy prior to entering this study.
• Cytoreduction with hydroxyurea Hydroxyurea can be initiated and continued for up
to 24 hours prior to the start of protocol therapy.
• Patients who relapsed while they are receiving cytotoxic therapy At least 14 days
must have elapsed since the completion of the last dose of chemotherapy,except
Intrathecal chemotherapy, and/or maintenance therapy such as vincristine,
mercaptopurine, methotrexate or glucocorticoids. There is no waiting period for
those relapsing on maintenance therapy.
C. Hematopoietic stem cell transplant: Patients who have experienced their relapse after a
HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host
Disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days
post-transplant at the time of enrollment.
D. Hematopoietic growth factors: It must have been at least 7 days since the completion of
therapy with G-CSF or other growth factors at the time of enrollment. It must have been at
least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
E. Biologic (anti-neoplastic agent): At least 7 days since the last dose of a biologic
agent. For agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse events
are known to occur. The duration of this interval must be discussed with the study chair
1. Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after
the last dose of monoclonal antibody. (i.e., blinatumomab = 6 hours,44 inotuzumab = 37
days, rituximab = 66 days)
2. Immunotherapy: At least 30 days after the completion of any type of immunotherapy,
e.g., tumor vaccines, CAR T cells.
F. XRT: Craniospinal XRT is prohibited during protocol therapy. No washout period is
necessary for radiation given to any extramedullary site other than CNS; ≥90 days must have
elapsed if prior total body irradiation (TBI) or craniospinal XRT.
G. Anthracyclines: Patients must have had a lifetime exposure of <400 mg/m2 of doxorubicin
equivalents of anthracyclines.
H. Proteasome inhibitors: Patients with a prior exposure to proteasome inhibitors (e.g.,
bortezomib, carfilzomib) are eligible as long as the patient demonstrated at least a
partial response to a proteasome inhibitor with chemotherapy combination.
-Renal and hepatic function
Patients must have adequate renal and hepatic functions as indicated by the following
laboratory values:
A. Adequate renal function defined as: Patient must have a calculated creatinine clearance
or radioisotope GFR 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender
B. Adequate Liver Function Defined as: Direct bilirubin ≤ 1.5 x upper limit of normal (ULN)
for age or normal (except in the presence of Gilbert's syndrome), AND alanine transaminase
(ALT) ≤ 5 x ULN for age. The hepatic requirements are waived for patients with known or
suspected liver involvement by leukemia or lymphoma. This must be reviewed by and approved
by the study chair or vice chair.
• Adequate Cardiac Function Defined as: Shortening fraction of more than or equal to 27%
by echocardiogram, OR ejection fraction of equal to or more than 50% by radionuclide
angiogram (MUGA).
• Reproductive Function A. Female patients of childbearing potential must have a
negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.
B. Female patients with infants must agree not to breastfeed their infants while on this
study.
C. Male and female patients of child-bearing potential must agree to use an effective
method of contraception approved by the investigator during the study and for a minimum of
6 months after study treatment.
• Informed Consent Patients and/or their parents or legal guardians must be capable of
understanding the investigational nature, potential risks and benefits of the study.
All patients and/or their parents or legal guardians must sign a written informed
consent. Age appropriate assent will be obtained per institutional guidelines. To
allow non-English speaking patients to participate in this study, bilingual health
services will be provided in the appropriate language when feasible.
• All institutional, FDA, and OHRP requirements for human studies must be met.
Exclusion Criteria:
Patients will be excluded if they have isolated CNS or testicular disease.
Patients will be excluded if they have ≥grade 2 peripheral sensory or motor neuropathy
(defined by the Modified "Balis" Pediatric Scale of Pediatric Neuropathies) at the time of
enrollment (see section 4.7.1.1).
Patients will be excluded if they have a known allergy or intolerance to any of the drugs
used in the study •except for PEG-asparaginase for which erwinia asparaginase may be
substituted
Patients will be excluded if they have a systemic fungal, bacterial, viral or other
infection that is exhibiting ongoing signs/symptoms related to the infection without
improvement despite appropriate antibiotics or other treatment. The patient needs to be off
pressors and have negative blood cultures for 48 hours.
Patients will be excluded if there is a plan to administer non-protocol chemotherapy,
radiation therapy, or immunotherapy during the study period.
Patients will be excluded if they have significant concurrent disease, illness, psychiatric
disorder or social issue that would compromise patient safety or compliance with the
protocol treatment or procedures, interfere with consent, study participation, follow up,
or interpretation of study results.
Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are
excluded.
Patients will be excluded if they have had a lifetime exposure of ≥400 mg/m2 doxorubicin
equivolents of anthracyclines (anthracycline equivalence to doxorubicin conversion see
appendix iv) .
Concomitant medications Investigational drugs: Patients currently receiving another
investigational drug are not eligible.
Anti-GVHD agents post transplant: patients who are receiving cyclosporine, tacrolimus or
other agents to prevent graft-versus-host disease post hematopoetic stem cell transplant
are not eligible.
CYP3A4 agents: patients who are currently receiving drugs that are strong inducers of
CYP3A4 are not eligible. Strong inducers of CYP3A4 should be avoided from 14 days prior to
enrollment to the end of the study. See appendix ii for a list of agents which fall into
this category.
Patients with Ph+ALL and Ph-like ALL who are currently receiving TKI therapy
Infants or Patients with Down Syndrome will be excluded in phase 2 of the study
Clinical Transplant-Related Long-term Outcomes of Alternative Donor Allogeneic Transplantation (BMT CTN 1702)
The purpose of this study is to determine if a search strategy of searching for an
HLA-matched unrelated donor for allogeneic transplantation if possible then an alternative
donor if an HLA-matched unrelated donor is not available versus proceeding directly to an
alternative donor transplant will result in better survival for allogeneic transplant
recipients within 2 years after study enrollment.
Patients fulfilling the inclusion criteria will be eligible for enrollment in this study.
Of those who consent, only patients who lack a suitable HLA-identical or 1 allele or
antigen mismatched related donors are evaluable. Patients with an HLA-identical sibling or
1 allele or antigen mismatched family member donor are evaluable as long as the center
deems the family member donor as unsuitable for other reasons. Patients may co-enroll with
other interventional or observational studies.
1. Patients of all ages with AML, ALL, MDS, NHL, HL, AA, or SCD are eligible.
2. Any planned conditioning regimen and GVHD prophylaxis approach is eligible.
3. Patients must be considered suitable allogeneic transplant candidates at the time of
enrollment based on medical history, physical examination, and available laboratory
tests. Specific testing for organ function is not required for eligibility but, if
available, these tests should be used by the treating physician to judge transplant
suitability.
4. Patient and physician must intend to proceed with allogeneic HCT within the next 6
months if a suitable donor is identified.
5. Center plans to follow the algorithm for alternative donor identification: (a) for
subjects who are Very Likely to find a MUD, attempt to identify a matched unrelated
donor; (b) for a subjects who are Very Unlikely to find a MUD, proceed expeditiously
to a haploidentical, cord blood or mismatched unrelated donor.
6. Signed informed consent, and assent if applicable. Consent may be signed prior to
completion of family typing but patients will only be considered evaluable upon
confirmation that there is no suitable HLA-identical or 1 allele or antigen mismatched
related donor available.
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies how well inotuzumab ozogamicin and post-induction chemotherapy
work in treating patients with high-risk B-cell lymphoblastic lymphoma (B-ALL), mixed
phenotype acute leukemia, and B-lymphoblastic lymphoma (B-LLy). Inotuzumab ozogamicin is a
monoclonal antibody, called inotuzumab, linked to a toxic agent called calicheamicin.
Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin to kill
them. Drugs used in chemotherapy, such as cyclophosphamide, cytarabine, doxorubicin,
daunorubicin, methotrexate, leucovorin, mercaptopurine, thioguanine, vincristine, and
pegaspargase, work in different ways to stop the growth of cancer cells, either by killing
the cells, by stopping them from dividing, or by stopping them from spreading.
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard
of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic
Leukemia (HR B-ALL). The goal of the part 1 of the study is to collect information about
leukemia and the effects of the first two phases of treatment, called Induction and
Consolidation on this cancer. Additionally, this study aims to investigate whether treating
both males and females with the same duration of chemotherapy maintains outcomes for males
who have previously been treated for 3 years from the start of Interim Maintenance in patient
with High Risk Favorable (HR-Fav) and HR B-ALL. Another aim is to understand the outcomes of
subjects with disseminated B-cell Lymphoblastic Leukemia (B LLy) receiving HR B-ALL therapy.
Finally, another goal of this study is to determine the outcomes of subjects with Mixed
Phenotype Acute Leukemia (MPAL) with a favorable early response to treatment using High Risk
B-cell Acute Lymphoblastic Leukemia therapy.
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility
studies (Part A) prior to treatment and enrollment on AALL1732. Note that central
confirmation of MPAL diagnosis must occur within 7 business days after enrollment for
MPAL patients. If not performed within this time frame, patients will be taken off
protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance
every patient should be offered participation in APEC14B1. B LLy patients may directly
enroll on AALL1732 and MUST submit eligibility studies as outlined.
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016
criteria) with > 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the
diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM
biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells if a bone marrow aspirate or biopsy cannot be
performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for
diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,
paraffin blocks), the methodology and criteria for immunophenotypic analysis to
establish the diagnosis of B-LLy defined by the submitting institution will be
accepted.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL
are eligible for AALL1731, regardless of NCI risk group).
• Patients with known Charcot-Marie-Tooth disease.
• With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for the
current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to
initiation of protocol therapy on AALL1732.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow
submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid
pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating women who plan to breastfeed their infants while on study and for 2 months
after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of study participation. For those
patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the
last dose of inotuzumab ozogamicin for females and 5 months after the last dose of
inotuzumab ozogamicin for males.
The design of the study incorporates the following features:
1. This is a phase II study to determine the safety and therapeutic potential of a new
transplant approach (disease-free survival, graft versus myeloma effect) and to evaluate
its toxicity profile (immediate toxicity, graft-versus-host disease, graft rejection,
mortality) in a patient population with severe congenital anemias.
2. The patient cohort to be studied: Those patients with severe sickle cell disease and
thalassemia who have risk factors for high mortality and morbidity related to their
disease
3. Transplant Conditioning Regimen - Immunosuppression without myeloablation: Patients will
receive conditioning sufficient to allow donor lympho-hematopoietic engraftment without
complete marrow ablation. If the graft is rejected, the patient will reconstitute
autologous marrow function. We will use a combination of low dose irradiation,
Alemtuzumab (Campath®), and sirolimus.
4. Peripheral blood hematopoietic progenitor cell (PBPC) transplant: An unmanipulated
peripheral blood stem cell collection from a filgrastim (G-CSF) stimulated HLA-matched
donor should improve the chance of engraftment because of the high stem cell dose (5 x
106/kg CD34+ cells) and the presence of donor lymphocytes. To reduce the risk of GVHD,
patients will receive sirolimus before and after the transplant. The sirolimus will be
tapered as necessary to minimize any graft versus host disease while still maintaining
adequate chimerism.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Prapti Patel
103509
All
18 Years to 45 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT02038478
STU 012013-015
Show full eligibility criteria
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Inclusion Criteria:
• Inclusion criteria •Recipient
Disease specific:
Sickle Cell Disease •Patients with sickle cell disease at high risk for disease related
morbidity or mortality, defined by having irreversible end-organ damage (A, B, C,D, or E)
or potentially reversible complication(s) not ameliorated by hydroxyurea (F):
A. Stroke defined as a clinically significant neurologic event that is accompanied by an
infarct on cerebral MRI OR an abnormal trans-cranial Doppler examination (≥200m/s); OR
B. Sickle cell related renal insufficiency defined by a creatinine level ≥1.5 times the
upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR
nephrotic syndrome OR creatinine clearance < 50mL/min OR requiring peritoneal or
hemodialysis. OR
C. Pulmonary hypertension as defined by tricuspid regurgitant jet velocity (TRV) of ≥
2.5m/s at least 3 weeks after a vaso-occlusive crisis; OR
D. Recurrent tricorporal priapism defined as at least two episodes of an erection lasting
≥4 hours involving the corpora cavernosa and corpus spongiosa; OR
E. Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL
at baseline; OR
F. Any one of the below complications
1. Vaso-occlusive crises
2. Acute chest syndrome
3. Osteonecrosis of 2 or more joints
4. Red cell alloimmunization
Thalassemia •Patients with thalassemia who have grade 2 or 3 iron overload,
determined by the presence of 2 or more of the following:
• portal fibrosis by liver biopsy inadequate chelation history (defined as failure to
maintain adequate compliance with chelation with desferroxamine initiated within 18
months of the first transfusion and administered subcutaneously for 8-10 hours at
least 5 days each week) hepatomegaly of greater than 2 cm below the costochondral
margin
Non-disease specific:
Ages ≥ 18 but ≤ 45
6/6 HLA matched family donor available
Ability to comprehend and willing to sign an informed consent, assent obtained from
minors
Negative serum pregnancy test
Inclusion criteria •Donor
6/6 HLA identical family donor
Weight > 20 kg (in so far that the weight difference between recipient and donor does
not exceed a reasonable likelihood of being able to obtain an adequate cell dose from
the donor within two aphereses)
Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts,
normotensive, and no history of stroke)
Ability to comprehend and willing to sign an informed consent
Exclusion Criteria:
Exclusion criteria •Recipient
Any of the following would exclude the subject from participating
ECOG performance status of 3 or more or Lanksy performance status of <40
Diffusion capacity of carbon monoxide (DLCO) <50% predicted (corrected for hemoglobin
and alveolar volume)
Baseline oxygen saturation of <85% or PaO2 <70
Left ventricular ejection fraction: <40% estimated by ECHO
Transaminases > 5x upper limit of normal for age
Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking
medication and progression of clinical symptoms) within one month prior to starting
the conditioning regimen
Major anticipated illness or organ failure incompatible with survival from PBSC
transplant
Pregnant or lactating
Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months)
Major ABO mismatch
Exclusion criteria •Donor
Any of the following would exclude the donor from participating
Pregnant or lactating
Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months)
HIV positive
Hemoglobin S > 50%, or beta thalassemia intermediate
A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)
This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have any of
the following types of cancer:
- advanced melanoma (6 months to <18 years of age),
- advanced, relapsed or refractory programmed death-ligand 1 (PD-L1)-positive malignant
solid tumor or other lymphoma (6 months to <18 years of age),
- relapsed or refractory classical Hodgkin lymphoma (rrcHL) (3 years to <18 years of age),
or
- advanced relapsed or refractory microsatellite-instability-high (MSI-H) solid tumors (6
months to <18 years of age).
Part 1 will find the maximum tolerated dose (MTD)/maximum administered dose (MAD), confirm
the dose, and find the recommended Phase 2 dose (RP2D) for pembrolizumab therapy. Part 2 will
further evaluate the safety and efficacy at the pediatric RP2D.
The primary hypothesis of this study is that intravenous (IV) administration of pembrolizumab
to children with either advanced melanoma; a PD-L1 positive advanced, relapsed or refractory
solid tumor or other lymphoma; advanced, relapsed or refractory MSI-H solid tumor; or rrcHL,
will result in an Objective Response Rate (ORR) greater than 10% for at least one of these
types of cancer.
• Between 6 months and <18 years of age (or between 3 years and <18 years of age for
rrcHL participants) on day of signing informed consent/assent (the first 3
participants dosed in Part 1 are to be ≥ 6 years of age)
• Histologically- or cytologically-documented, locally-advanced, or metastatic solid
malignancy or lymphoma that is incurable and has failed prior standard therapy, or for
which no standard therapy exists, or for which no standard therapy is considered
appropriate
• Any number of prior treatment regimens
• Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue
sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor
lesion not previously irradiated
• Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or
lymphoma
• Measurable disease based on RECIST 1.1 (Or based on IWG [Cheson, 2007] [i.e.,
measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrcHL
participants)
• Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive
evaluable disease may be enrolled
• Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of
age; or Karnofsky score ≥50 for participants >16 years of age
• Adequate organ function
• Female participants of childbearing potential should have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication
• Female participants of childbearing potential must be willing to use 2 methods of
contraception or be surgically sterile, or abstain from heterosexual activity for the
course of the study through 120 days after the last dose of study medication
• Male participants of reproductive potential must agree to use an adequate method of
contraception starting with the first dose of study medication through 120 days after
the last dose of study medication
Exclusion Criteria:
• Currently participating and receiving study therapy in, or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the date of allocation/randomization
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
of immunosuppressive therapy within 7 days prior to the date of
allocation/randomization
• Prior systemic anti-cancer therapy including investigational agent within 2 weeks
prior to study Day 1 or not recovered from adverse events due to a previously
administered agent
• Prior radiotherapy within 2 weeks of start of study treatment
• Known additional malignancy that is progressing or requires active treatment with the
exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or
carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially
curative therapy, or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Tumor(s) involving the brain stem
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in past 2 years;
replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is acceptable
• Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
• Active infection requiring systemic therapy
• Pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial through 120 days after the last dose of study
medication
• Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1
(anti-PD-L1), anti-PD-L2 agent, or any agent directed to another stimulatory or
inhibitory T-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [CTLA-4],
OX-40, CD137)
• Human immunodeficiency virus (HIV)
• Hepatitis B or C
• Known history of active tuberculosis (TB; Bacillus tuberculosis)
• Received a live vaccine within 30 days of planned start of study medication
• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic
stem cell transplantation within the last 5 years. (Participants who have had an
allogeneic hematopoietic transplant >5 years ago are eligible as long as there are no
symptoms of Graft Versus Host Disease [GVHD].)
• History or current evidence of any condition, therapy, or laboratory abnormality, or
known severe hypersensitivity to any component or analog of the trial treatment, that
might confound the results of the trial, or interfere with the participant's
participation for the full duration of the study
• Known psychiatric or substance abuse disorders that would interfere with the
requirements of the study
Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) (STARTRK-2)
This is an open-label, multicenter, global Phase 2 basket study of entrectinib (RXDX-101) for
the treatment of patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene
fusion. Patients will be assigned to different baskets according to tumor type and gene
fusion.
• Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic
solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement
•Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene
rearrangement of interest may be eligible provided they meet all other
inclusion/exclusion criteria
• For patients enrolled via local molecular testing, an archival or fresh tumor tissue
(unless medically contraindicated) is required to be submitted for independent central
molecular testing at Ignyta's CLIA laboratory post-enrollment
• Measurable or evaluable disease
• Patients with CNS involvement, including leptomeningeal carcinomatosis, which is
either asymptomatic or previously-treated and controlled, are allowed
• Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1,
or ALK inhibitors in patients who have tumors that harbor those respective gene
rearrangements)
•Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged
NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are
prohibited.
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior
chemotherapy or small molecule targeted therapy
• At least 4 weeks must have elapsed since completion of antibody-directed therapy
• Prior radiotherapy is allowed if more than 14 days have elapsed since the end of
treatment
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and minimum life
expectancy of 4 weeks
• Adequate organ function as defined per protocol
• Ability to swallow entrectinib intact
• Other protocol specified criteria
Exclusion Criteria:
• Current participation in another therapeutic clinical trial
• Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in
patients who have tumors that harbor those respective gene rearrangements
•Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged
NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are
prohibited.
• History of other previous cancer that would interfere with the determination of safety
or efficacy
• Incomplete recovery from any surgery
• History of non-pharmacologically induced prolonged QTc interval
• History of additional risk factors for torsade de pointes
• Peripheral neuropathy Grade ≥ 2
• Known active infections
• Active gastrointestinal disease or other malabsorption syndromes
• Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase
inhibitor-induced pneumonitis
• Other protocol specified criteria
Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine in Adult Patients With Acute Myeloid Leukemia (AML)
The purpose of the phase 1b/2 study is to determine whether Onvansertib given orally daily
for 5 consecutive days every 28 days is safe and tolerable in adult patients who have
relapsed/refractory Acute Myeloid Leukemia (AML), or are ineligible for intensive induction
therapy, and to determine the maximum tolerated dose and recommended phase 2 dose of
Onvansertib in combination with decitabine or Onvansertib in combination with low-dose
cytarabine. In the phase 2 portion of the study, Onvansertib in combination with decitabine
will be studied to provide further data on the safety profile of the combination and to
preliminarily assess the activity of the chosen combination in patients with untreated AML
who are not candidates for aggressive induction therapy, or who have received one prior
treatment for their AML.
1. Disease Status and Prior Therapy:
1. Histologically confirmed AML with >20% blasts
2. Phase 1b: Participants with AML who are refractory to or have relapsed after
initial treatment for their disease, with no more than three prior lines of
therapy. Participants who have received prior treatment with cytarabine or
decitabine are not excluded.
3. Phase 2:
i. Participants with AML who are refractory to, or have relapsed after, initial
treatment for their disease, with no more than one prior line of therapy, and are
judged not to be candidates for re-induction therapy that includes hematopoietic cell
transplantation. Participants who have received prior cytarabine or decitabine are not
excluded.
OR
ii. Participants with newly diagnosed, untreated AML ineligible for, or who have
refused, standard intensive induction therapy
2. Age ≥18 years
3. ECOG performance status ≤2
4. Participants must be willing and able to review, understand, and provide written
consent before starting any study-specific procedures or therapy.
5. All men and women must agree to practice effective contraception during the entire
study period and after discontinuing study drug, unless documentation of infertility
exists
1. Sexually active, fertile women must use two effective forms of contraception
(abstinence, intrauterine device, oral contraceptive, or double barrier device)
from the time of informed consent and until at least 6 months after discontinuing
study drug
2. Sexually active men and their sexual partners must use effective contraceptive
methods from the time of participant informed consent and until at least 3 months
after discontinuing study drug
Exclusion Criteria:
1. Treatment-related AML or acute promyelocytic leukemia (APL)
2. Active malignancies within 12 months with the exception of those with a negligible
risk of metastasis or death
3. Clinical evidence of active central nervous system leukemia at the time of screening
4. Alanine aminotransferase and/or aspartate aminotransferase ≥2.5 x upper limit of
normal (ULN)
5. Total bilirubin > 2.0 mg/dL (or > 3.0 mg/dL in participants with documented Gilbert
syndrome)
6. Serum creatinine ≥2.0 mg/dL
7. New York Heart Association Class III or IV heart disease, active ischemia or any other
uncontrolled cardiac condition, or hypertensive or metabolic condition
8. Myocardial infarction in the previous 12 weeks (from the start of treatment)
9. Resting left ventricular ejection fraction <50% at the time of screening
10. QT (Interval from the beginning of the QRS complex to the end of the T wave on an
electrocardiogram) interval with Fridericia's correction [QTcF] >450 milliseconds. The
QTcF should be calculated as the arithmetic mean of the QTcF on triplicate ECGs. In
the case of potentially correctible causes of QT prolongation (e.g., medications,
hypokalemia), the triplicate ECG may be repeated once during screening and that result
may be used to determine eligibility.
11. Active and uncontrolled disease (other than AML) or infection as judged by the
treating physician
12. Treatment with systemic therapy for the primary disease within 14 days (except for
hydroxyurea or isolated doses of cytarabine or decitabine for white blood cell
control)
13. Grade 2 or greater toxicities from prior therapy, except for Grade 2 toxicities that
are not expected to resolve and that in the judgment of the Investigator do not pose a
significant safety risk to subject participation.
14. Participants with any other medical condition, including mental illness or substance
abuse, deemed by the Investigator to be likely to interfere with the participant's
ability to sign the informed consent form or his/her ability to cooperate and
participate in the study, or to interfere with the interpretation of the results.
Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
This randomized phase III trial studies how well imatinib mesylate and combination
chemotherapy work in treating patients with newly diagnosed Philadelphia chromosome positive
acute lymphoblastic leukemia. Imatinib mesylate may stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving imatinib mesylate and
combination chemotherapy may work better in treating patients with Philadelphia chromosome
positive acute lymphoblastic leukemia.
• For patients enrolled on AALL08B1 or APEC14B1 (if open for ALL patients) prior to
enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled
• For patients who have not previously enrolled on AALL08B1 or APEC14B1 (if open
for ALL patients) prior to enrollment on AALL1631, a baseline diagnostic sample
must be available to develop an MRD probe
• In addition, laboratory reports detailing evidence of BCR-ABL1 fusion must be
submitted for rapid central review within 72 hours of study enrollment
• Newly diagnosed de novo ALL (B-ALL or T-ALL) with definitive evidence of BCR-ABL1
fusion by karyotype, fluorescence in situ hybridization (FISH) and/or reverse
transcriptase (RT)-PCR
• Patient must have previously started induction therapy, which includes vincristine, a
corticosteroid, pegaspargase, with or without anthracycline, and/or other standard
cytotoxic chemotherapy
• Patient has not received more than 14 days of multiagent induction therapy beginning
with the first dose of vinCRIStine
• Patient may have started imatinib prior to study entry but has not received more than
14 days of imatinib
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2
• Direct bilirubin =< 2.0 mg/dL
• Shortening fraction of >= 27% by echocardiogram
• Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
• Corrected QT interval, QTc < 480 msec
• Note: Repeat echocardiogram is not required if echocardiogram was obtained within
21 days of study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2
• Serum creatinine within normal limits based on age/gender, as follows:
• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
Exclusion Criteria:
• Known history of chronic myelogenous leukemia (CML)
• ALL developing after a previous cancer treated with cytotoxic chemotherapy
• Active, uncontrolled infection, or active systemic illness that requires ongoing
vasopressor support or mechanical ventilation
• Down syndrome
• Pregnancy and breast feeding
• Female patients who are pregnant; a pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
• Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart
block
• Prior treatment with dasatinib, or any BCR-ABL1 inhibitor other than imatinib
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met