Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Ascertain the Optimal Starting Dose of Mircera Given Subcutaneously for Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.
Ascertain the starting dose of Mircera given subcutaneously for the maintenance treatment of
anemia in pediatric participants with chronic kidney disease (CKD) on dialysis or not yet on
dialysis when switching from stable subcutaneous (SC) maintenance treatment with epoetin
alfa, epoetin beta, or darbepoetin alfa.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Raymond Quigley
15874
All
3 Months to 17 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03552393
STU 022018-037
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Pediatric participants 3 months to 17 years of age with clinically stable chronic
renal anemia
• CKD with estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2
(determined by the Bedside Schwartz formula) or dialysis treatment for at least 8
weeks before the first dose of Mircera
• For participants on peritoneal dialysis (PD): a weekly Kt/V≥ 1.8
• For participants on HD: adequate HD, urea reduction ratio (URR) > 65% or Kt/V > 1.2
for participants on HD three times per week.
Participants with fewer than or more than three HD sessions per week should have a weekly
Kt/V≥ 3.6.
• Baseline Hb concentration 10.0-12.0 g/dL determined from the mean of two Hb values
measured at Visit 1 (Week -3) and Visit 2 (Week -1)
• Stable SC maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa
with the same dosing interval for at least 6 weeks before the first dose of Mircera
• Stable dose of epoetin alfa, epoetin beta, or darbepoetin alfa treatment with no
weekly dose change > 25% (increase or decrease) for at least 4 weeks before the first
dose of Mircera
• Adequate iron status defined as ferritin≥100 ng/mL or transferrin saturation (TSAT)≥
20% (or percentage of hypochromic red cells < 10%); mean of two values measured during
screening.
Exclusion Criteria:
• Overt gastrointestinal bleeding within 8 weeks before screening or during the
screening period
• RBC transfusions within 8 weeks before screening or during the screening period
• Hemoglobinopathies (e.g., homozygous sickle-cell disease, thalassemia of all types)
Hemolytic anemia, Active malignant disease
• PD subjects with an episode of peritonitis within the past 30 days prior to screening
and/or during the screening period
• Uncontrolled or symptomatic inflammatory disease (e.g., systemic lupus erythematosus)
• Uncontrolled hypertension as assessed by the investigator
• Epileptic seizures within 3 months prior to screening and during the screening period
• Administration of any investigational drug within 4 weeks prior to screening or
planned during the study
• Severe hyperparathyroidism (intact parathyroid hormone [PTH]≥ 1000 pg/mL or whole PTH≥
500 pg/mL) or biopsy-proven bone marrow fibrosis
• Kidney transplant with use of immunosuppressive therapies known to exacerbate anemia
• Known hypersensitivity to recombinant human erythropoietin (EPO), polyethylene glycol,
or any constituent of the study drug formulation
• Anti-EPO antibody (AEAB)-mediated pure red cell aplasia (PRCA) or history of AEAB
mediated PRCA or positive AEAB test result in the absence of PRCA
• High likelihood of early withdrawal or interruption of the study (e.g., planned living
donor kidney transplant within 5 months of study start)
• Planned elective surgery during the entire study period
Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
This is a Phase 1/2, open-label, first-in-human study designed to evaluate the safety,
tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib
(also known as LOXO-292) administered orally to patients with advanced solid tumors,
including RET-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors
with RET activation.
For Phase 1
• Patients with a locally advanced or metastatic solid tumor who:
• have progressed on or are intolerant to standard therapy, or
• no standard therapy exists, or in the opinion of the Investigator, are not
candidates for or would be unlikely to tolerate or derive significant clinical
benefit from standard therapy, or
• decline standard therapy
• Prior MKIs with anti-RET activity are allowed.
• A RET gene alteration is not required initially. Once adequate PK exposure is
achieved, evidence of RET gene alteration in tumor and/or blood is required as
identified through molecular assays, as performed for clinical evaluation.
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
appropriate to tumor type.
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance
Score (LPS) ≥ 40% (age < 16 years) with no sudden deterioration 2 weeks prior to the
first dose of study treatment.
• Adequate hematologic, hepatic and renal function.
• Life expectancy of at least 3 months.
For Phase 2
As for phase 1 with the following modifications:
•For Cohort 1 (up to 250 patients): Subjects must have received prior standard therapy
appropriate for their tumor type and stage of disease, or in the opinion of the
Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate
standard of care therapy.
• Cohorts 1 and 2: enrollment will be restricted to patients with evidence of a RET gene
alteration in tumor.
• Cohorts 1 and 2: at least one measurable lesion as defined by RECIST 1.1 or RANO, as
appropriate to tumor type and not previously irradiated.
• Cohorts 3 and 4: Enrollment closed.
• Cohort 5: (up to 200 patients):
• Cohorts 1 and 2 without measurable disease;
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with
neuroendocrine features/differentiation, or poorly differentiated thyroid cancers
with other RET alteration/activation may be allowed with prior Sponsor approval;
• cfDNA positive for a RET gene alteration not known to be present in a tumor
sample.
• Cohort 6 (up to 50 patients):
• Patients who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued
another RET inhibitor due to intolerance may be eligible with prior Sponsor
approval.
Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver.
• Cohorts 3 and 4: Enrollment closed.
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor
Notes:
Patients otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET
inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.
•Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5
half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292
(selpercatinib). In addition, no concurrent investigational anti-cancer therapy is
permitted.
Note:
Potential exception for this exclusion criterion will require a valid scientific
justification and approval from the Sponsor.
• Major surgery (excluding placement of vascular access) within 4 weeks prior to planned
start of LOXO-292 (selpercatinib).
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned
start of LOXO-292 (selpercatinib), with the exception of patients receiving radiation
to more than 30% of the bone marrow or with a wide field of radiation, which must be
completed at least 4 weeks prior to the first dose of study treatment.
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
starting study treatment with the exception of alopecia and Grade 2, prior
platinum-therapy related neuropathy.
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated
spinal cord compression. Patients are eligible if neurological symptoms and CNS
imaging are stable and steroid dose is stable for 14 days prior to the first dose of
LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28
days, 14 days if stereotactic radiosurgery [SRS].
• Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or
prolongation of the QT interval corrected (QTcF) > 470 msec.
• Required treatment with certain strong CYP3A4 inhibitors or inducers and certain
prohibited concomitant medications.
Drug: LOXO-292 (selpercatinib)
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib
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 (recurrent) or do not respond
to treatment (refractory). 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, 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, Intravascular Large B-Cell Lymphoma, Large B-Cell Lymphoma With IRF4 Rearrangement, 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, 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, High Grade B-Cell Lymphoma, Not Otherwise Specified, Lymphoid Leukemia, HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Recurrent Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma, Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
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 the 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 than 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.
• 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.
• Patients who have received > 72 hours of hydroxyurea.
• 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 known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• 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.
Clinical Trial to Evaluate CT053 in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2)
A phase 1b, open label, multi-center, Clinical Study of Chimeric Antigen Receptor T Cells
targeting BCMA in patients with relapsed and or refractory multiple myeloma.
1. Voluntarily signed consent;
2. Age of ≥ 18 and ≤ 80 years;
3. Received sufficient prior lines of myeloma therapy;
4. Received treatment with at least one proteasome inhibitor, one IMiD and daratumumab.
5. The patients should have measurable disease per IMWG definition.
6. Estimated life expectancy > 12 weeks;
7. ECOG performance score 0-1;
8. Patients should have reasonable CBC counts, renal and hepatic functions;
9. Sufficient venous access for leukapheresis collection, and no other contraindications
to leukapheresis;
10. Women of childbearing age must undergo a serum pregnancy test with negative results
before screening, and are willing to use effective and reliable method of
contraception for at least 6 months after T cell infusion;
11. Men must be willing to use effective and reliable method of contraception for at least
6 months after T cell infusion.
Exclusion Criteria:
1. Pregnant or lactating women;
2. HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection;
3. Any uncontrolled active infection;
4. AEs from previous treatment that have not recovered;
5. Patients who have had anti-BCMA therapy;
6. Patients who have graft versus host disease (GvHD);
7. Patients have received stem cell transplantation less than 12 weeks before
leukapheresis;
8. Patients have received any anti-cancer treatment before leukapheresis;
9. Patients have received steroids before leukapheresis or lymphodepletion;
10. Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS
(polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin
changes) syndrome or clinically significant symptomatic immunoglobulin light chain
(AL) amyloidosis with evidence of end-organ damage;
11. Patients have been administered live attenuated vaccine before leukapheresis or
lymphodepletion;
12. Patients allergic to Flu, Cy, tocilizumab, dimethyl sulfoxide (DMSO) or CT053 CAR BCMA
T cell;
13. Patients have clinical significant cardiac conditions that researchers believe that
participating in this clinical trial may endanger the health of the patients;
14. Patients have clinical significant pulmonary conditions;
15. Patients are known to have active autoimmune diseases including but not limited to
psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive
therapy;
16. Patients with second malignancies in addition to MM are not eligible;
17. Patients have central nervous system (CNS) metastases or CNS involvement;
18. Patients have significant neurologic disorders;
19. Patients are unable or unwilling to comply with the requirements of clinical trial;
20. Patients have received major surgery prior to leukapheresis or prior to
lymphodepletion.
APVO436 is being studied in this Phase 1/1b, open-label, multi-center, dose-escalation study
to evaluate the safety, pharmacokinetic/pharmacodynamic and clinical activity of APVO436
monotherapy in: 1) patients with AML that have relapsed on prior therapy or are refractory to
therapy and are not candidates for intensive chemotherapy or transplant, and 2) patients with
MDS that have > 5% blasts in the bone marrow or blasts in the peripheral blood who have also
failed prior therapy with an hypomethylating agent (HMA).
The primary objective of the Phase 1 part of the study is to determine the recommended dose
of APVO436 administered intravenously to patients with AML or MDS. The primary objective of
the Phase 1b part of the study is to evaluate the clinical activity of APVO436 in patients
with AML or MDS.
1. Signed informed consent. Consent must be obtained prior to any study-related
procedure.
2. Age ≥ 18 years
3. Histologically confirmed AML or MDS:
1. AML •relapsed or refractory AML and refuses or is not a candidate for intensive
chemotherapy (due to prior failure or not eligible due to expected intolerance)
or allogeneic transplant
2. MDS •relapsed or refractory MDS with > 5% blasts in the marrow or any blasts in
the peripheral blood. Patients must have failed prior treatment with an HMA
(azacitidine, decitabine, or other HMA agent); failure is defined as intolerance
to HMA, lack of response [no complete remission (CR) by at least 6 cycles], or
have IWG-defined progressive disease during or after treatment with an HMA.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
5. Life expectancy of > 2 months in the Investigator's opinion
6. White blood cells (WBC) ≤ 25,000 cells/mm3 (may receive hydroxyurea to bring WBC count
down prior to and during the first cycle of treatment with study drug if necessary)
7. Creatinine ≤ 2 × upper limit of normal (ULN)
8. Adequate liver test parameters: total bilirubin < 2.5 × ULN (if disease related or
secondary to Gilbert's disease, then total bilirubin < 3.5 mg/dL), aspartate
aminotransferase (AST), and alanine aminotransferase (ALT) < 3 × ULN
9. Prothrombin time (PT) / international normalized ratio (INR) and partial
thromboplastin time (PTT) < 1.5 × ULN
10. Patients and partners of childbearing potential must be willing to use adequate
contraception during the study and for 2 months after last study drug administration.
Adequate contraception means less than 1% chance of pregnancy may occur with proper
use of the method(s).
Exclusion Criteria:
1. Any central nervous system (CNS) (cerebral/meningeal) disease related to underlying
malignancy
2. History of seizures
3. Acute promyelocytic leukemia
4. Prior anti-CD123 therapy outside of this study
5. Any clinically significant graft-versus-host disease (GVHD) secondary to prior
allogenic transplant. Patients must be >90 days from transplant and have been on no
immunosuppressive therapy for >30 days. Topical corticosteroids for minor skin rash
(<5% body surface area) is acceptable. Prior solid organ transplant is acceptable
provided the patient is on no immunosuppressive therapy.
6. Any therapy or experimental treatment for MDS or AML within 7 days of the first dose
of study drug. Must have recovered to Grade ≤ 1 from any Grade 2 to 4 toxicity from
previous treatment. The use of hydroxyurea is acceptable and does not exclude the
patient.
7. Active, uncontrolled infection requiring systemic therapy. If the infection is
controlled or has resolved, maintenance and/or prophylactic systemic antimicrobials
are permitted.
8. Major surgery within 3 weeks prior to first dose of study drug
9. Known to be positive for HIV, hepatitis B virus surface antigen (HBsAg), hepatitis B
core antibody (HBcAb), or hepatitis C virus (HCV)
10. Pregnant or breast feeding
11. Any other active systemic malignancies. Exceptions: noninvasive non-melanoma skin
cancer, in situ carcinoma, cervical intraepithelial neoplasia, and breast or prostate
cancer that is well controlled with anti-hormonal therapy
12. Any current autoimmune disorder requiring immunosuppressive therapy
13. Requires more than a replacement dose of corticosteroids (i.e., > 10 mg/day of
prednisone or equivalent)
14. Any uncontrolled medical condition, including but not limited to:
1. Symptomatic congestive heart failure ≥ Class III (New York Heart Association
Functional Classification)
2. Uncontrolled hypertension
3. Unstable angina
4. Myocardial infarction within previous 6 months
5. Clinically significant arrhythmias not controlled by medication
6. Uncontrolled metabolic disorders such as hypercalcemia
15. Substance use disorder, psychiatric, cognitive, or any other condition that, in the
opinion of the Investigator, would pose a risk to the patient's safety, may compromise
the patient's ability to understand and comply with the protocol or provide informed
consent, or interfere with the study evaluation
16. Any difficulty complying with protocol requirements that may increase the risk
associated with study participation or study drug administration, or may cause a
safety concern for the patient
A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
This phase III trial compares standard chemotherapy to therapy with CPX-351 and/or
gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3
mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab
ozogamicin, 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. CPX-351 is made up
of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone
marrow longer and could be less likely to cause heart problems than traditional anthracycline
drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an
abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that
carry instructions for development, functioning, growth and reproduction) inside each cell
that tell the cell what to do and when to grow and divide. FLT3 plays an important role in
the normal making of blood cells. This gene can have permanent changes that cause it to
function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function
of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to
compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people
with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or
bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or
other FLT3 mutations and 3) to study changes in heart function during and after treatment for
AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in
treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
• All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part
A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens
must be done according to the Manual of Procedures). Risk stratification will not be
possible without the submission of viable samples. Given there are multiple required
samples, bone marrow acquisition techniques such as frequent repositioning or
performing bilateral bone marrow testing should be considered to avoid insufficient
material for required studies. Consider a repeat marrow prior to starting treatment if
there is insufficient diagnostic material for the required studies
• Patients must be less than 22 years of age at the time of study enrollment
• Patient must be newly diagnosed with de novo AML according to the 2016 World Health
Organization (WHO) classification with or without extramedullary disease
• Patient must have 1 of the following:
• >= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
• In cases where extensive fibrosis may result in a dry tap, blast count
can be obtained from touch imprints or estimated from an adequate bone
marrow core biopsy
• < 20% bone marrow blasts with one or more of the genetic abnormalities
(sample obtained within 14 days prior to enrollment)
• A complete blood count (CBC) documenting the presence of at least 1,000/uL
(i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a
WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells
(blasts) if a bone marrow aspirate or biopsy cannot be performed (performed
within 7 days prior to enrollment)
• ARM C: Patient must be >= 2 years of age at the time of Late Callback
• ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular
Oncology
• ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
• ARM C: Females of reproductive potential must agree to use effective contraception
during treatment and for at least 6 months after the last dose of gilteritinib
• ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib
and for 2 months after the last dose of gilteritinib
• ARM C: Males of reproductive potential must agree to use effective contraception
during treatment and for at least 4 months after the last dose of gilteritinib
• ARM D: Patient must be >= 2 years of age at the time of Late Callback
• ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating
mutations as reported by Foundation Medicine
• ARM D: Females of reproductive potential must agree to use effective contraception
during treatment and for at least 6 months after the last dose of gilteritinib
• ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib
and for 2 months after the last dose of gilteritinib
• ARM D: Males of reproductive potential must agree to use effective contraception
during treatment and for at least 4 months after the last dose of gilteritinib
• NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who
transfer to Arm C or Arm D are not eligible
• NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
• NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
• NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to
diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental
retardation)
• NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would
prevent computer use or recognition of visual test stimuli
• 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.
Exclusion Criteria:
• Patients with myeloid neoplasms with germline predisposition are not eligible
• Fanconi anemia
• Shwachman Diamond syndrome
• Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
• Any other known bone marrow failure syndrome
• Any concurrent malignancy
• Juvenile myelomonocytic leukemia (JMML)
• Philadelphia chromosome positive AML
• Mixed phenotype acute leukemia
• Acute promyelocytic leukemia
• Acute myeloid leukemia arising from myelodysplasia
• Therapy-related myeloid neoplasms
• Administration of prior anti-cancer therapy except as outlined below:
• Hydroxyurea
• All-trans retinoic acid (ATRA)
• Corticosteroids (any route)
• Intrathecal therapy given at diagnosis
• In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be
avoided from the time of enrollment until it is determined whether the patient
will receive gilteritinib. Patients receiving gilteritinib will be required to
avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the
study treatment
• 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
• ARM D: Patients with congenital long QT syndrome or congenital heart block are not
eligible for this treatment arm
Venetoclax and Selinexor in Treating Patients With Relapsed or Refractory High Risk Hematologic Malignancies
This phase Ib trial studies the toxicity and dosing of venetoclax in combination with
selinexor, and how well the combination works in treatment of patients with high risk
hematologic malignancies such as diffuse large B-cell lymphoma and acute myeloid leukemia
that has come back (recurrent) or does not respond to initial treatment (refractory).
Venetoclax functions by inhibiting a protein in the body called bcl-2, which is involved in
slowing down the normal process by which old cells in the body are cleared (called
apoptosis). Selinexor functions by trapping "tumor suppressing proteins" within the cell and
causing the cancer cells to die or stop growing. This study examines the effects, if any, of
selinexor and venetoclax on high risk hematologic malignancies and on the body, including any
side-effects.
• Written informed consent in accordance with federal, local, and institutional
guidelines. The patient must provide informed consent prior to the first screening
procedure.
• Age ≥ 18 years
• Life expectancy > 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed diagnosis of one of the following, in accordance with WHO
diagnostic criteria:
• Escalation:
• Diffuse Large B-cell Lymphoma (DLBCL, including primary mediastinal large B cell
lymphoma, T cell rich B cell lymphoma, and high-grade B cell lymphoma NOS).
Patients with Burkitt's, lymphoblastic lymphoma, follicular lymphoma, and mantle
cell lymphoma are not included. OR
• Acute Myeloid Leukemia (AML)
• Expansion:
• Diffuse Large B-cell Lymphoma and acute myeloid leukemia as above.
• VEN Refractory expansion cohort (Diffuse Large B-cell Lymphoma and acute myeloid
leukemia only): Patients must have previously received and failed venetoclax
therapy (either monotherapy or combination) during their treatment course (i.e.,
patients may receive non-VEN therapy immediately prior to enrollment on this
study). Treatment failure is defined as evidence of disease progression after ≥ 1
cycle (four weeks) of full-intensity venetoclax-based therapy (i.e., 28 days
exclusive of ramp-up. Patients that require dose reductions due to intolerance
may be considered for this cohort after discussion with the sponsor.)
• Relapsed or refractory following ≥ 1 line(s) of prior therapy
• Patients that relapse ≥ 3 months after allogeneic hematopoietic cell transplantation
(HCT) are eligible.
• Female patients of childbearing potential must agree to use two methods of
contraception (including one highly effective and one effective method of
contraception) and have a negative serum pregnancy test at screening. Male patients
must use an effective barrier method of contraception if sexually active with a female
of childbearing potential. For both male and female patients, effective methods of
contraception must be used throughout the study and for 3 months following the last
dose of study treatment.
• For leukemia and DLBCL with known or suspected marrow involvement, patients must have
at least 10-15 mL of bone marrow aspirate material obtained within 14 days of
beginning treatment on this study. Patients with DLBCL must have 3-5 unstained slides,
or tissue block, available for evaluation within 14 days of study enrollment in the
expansion cohorts. DLBCL patients enrolled during the escalation phase must have
blocks available for submission within 28 days of beginning treatment.
• CBC testing must confirm adequate marrow reserve, as demonstrated by:
• DLBCL: Hgb ≥ 10g/dL, platelets ≥ 75,000 cells/mm3 , ANC ≥ 1,000 cells/mm3
• Adequate organ function, as demonstrated by:
• Total bilirubin < 1.5 x upper limit of normal (ULN) (except patients with
Gilbert's syndrome (hereditary indirect hyperbilirubinemia), who must have a
total bilirubin of < 3 x ULN, and
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2
x ULN
• Calculated creatinine clearance > 50 mL/min (per the Cockcroft-Gault formula).
• Patients with laboratory evidence of liver or kidney dysfunction secondary to
underlying disease, that is expected to reverse with treatment, may be enrolled after
discussion with the sponsor/investigator.
Exclusion Criteria:
• Patients who are pregnant or lactating
• Patients who received any systemic anticancer therapy including investigational agents
or radiation ≤3 weeks (or ≤5 half-lives of the drug [whichever is shorter]) prior to
C1D1. Hydroxyurea is permitted for up to 14 days in AML patients
• Inadequate recovery from toxicity attributed to prior anti-cancer therapy. With the
exception of alopecia or fatigue, patients must have recovered to baseline or ≤ Grade
1 (NCI-CTCAE v4.03) residual toxicity prior to first dose of protocol-indicated
treatment.
• Participation in another clinical trial with any investigational drug within 14 days
prior to study enrollment.
• Patients included in the VEN refractory cohort that have discontinued venetoclax
therapy (either monotherapy or combination) due to toxicity or hypersensitivity,
including prior history of grade 3/4 TLS during prior VEN exposure
• In dose expansion cohorts, except venetoclax refractory cohort, no prior treatment
with SINE compounds, another XPO1 inhibitor, or BCL-2 inhibitors.
• Active GVHD requiring calcineurin inhibitors or steroid dosing ≥ 10mg/day prednisone
(or equivalent) or < 3 months from allogenic hematopoietic cell transplant (HCT).
• Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,
antivirals, or antifungals within one week prior to first dose; however, prophylactic
use of these agents is acceptable even if parenteral.
• Major surgery within 2 weeks of first dose of study drug.
• Any life-threatening illness, medical condition or organ system dysfunction which, in
the investigator's opinion, could compromise the patient's safety.
• Unstable cardiovascular function:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (i.e., ventricular
tachycardia on anti-arrhythmia therapy are excluded; 1st degree AV block or
asymptomatic LAFB/RBBB will not be excluded), or
• Congestive heart failure (CHF) of NYHA Class ≥3, or
• Myocardial infarction (MI) within 3 months.
• Known active Hepatitis B or Hepatitis C infection (Hepatitis testing is not required
as part of this study).
• Known human immunodeficiency virus (HIV) infection (HIV testing is not required as
part of this study).
• Subject has received the following ≤ 7 days prior to Cycle 1, Day 1: Strong and
moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's
wort.
• Subject has received the following ≤ 5 days prior to Cycle 1, Day 1: Strong and
moderate CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin.
• Subject has consumed grapefruit, grapefruit products, Seville oranges (including
marmalade containing Seville oranges) or Starfruit ≤ 3 days prior to Cycle 1, Day 1.
• Inability to swallow oral medication; or the presence of a poorly controlled
gastrointestinal disease, disorder, syndrome, or dysfunction that could significantly
affect the absorption of oral study drug •e.g. Crohn's disease, ulcerative colitis,
chronic diarrhea (defined as > 4 loose stools per day), malabsorption syndrome, or
bowel obstruction.
• Inability or unwillingness to take required and recommended medications intended to
prevent and treat potential adverse events of tumor lysis syndrome (TLS), nausea and
vomiting, loss of appetite, and fatigue.
• Patients unwilling to comply with the protocol
Drug: Venetoclax, Drug: Selinexor
Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Diffuse Large B-Cell Lymphoma
Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Haemostasis During Surgery in Paediatric Subjects
This is a prospective, randomized, active-controlled, single-blind, parallel group clinical
trial to evaluate the safety and efficacy of FS Grifols as an adjunct to hemostasis during
surgery in pediatric subjects.
Pediatric subjects (<18 years of age) requiring an elective (non-emergent), open
(non-laparoscopic), pelvic, abdominal, or thoracic (non-cardiac) surgical procedure, wherein
a target bleeding site (TBS) is identified, and a topical hemostatic agent is indicated, will
be eligible to participate in the clinical trial.
The study treatments will be applied on the cut parenchymous surface of a solid organ (ie,
liver) and in soft tissue (ie, fat, muscle, or connective tissue).
Call 214-648-5005 studyfinder@utsouthwestern.edu
Dev Desai
97218
All
up to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03461406
STU 062018-049
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
Pre-operative:
1. Less than 18 years of age.
2. Requires an elective (non-emergent), open (non-laparoscopic), pelvic, abdominal, or
thoracic (non-cardiac) surgical procedure.
3. Subject and/or subject's legal guardian is willing to give permission for the subject
to participate in the clinical trial and provide written informed consent for the
subject. In addition, assent must be obtained from pediatric subjects who possess the
intellectual and emotional ability to comprehend the concepts involved in the clinical
trial.
Intra-operative:
4. Presence of an appropriate (as defined in inclusion criterion 5) parenchymous or soft
tissue TBS identified intra-operatively by the investigator (the surgeon).
5. TBS has Grade 1 (mild) or Grade 2 (moderate) bleeding intensity according to the
investigator's (the surgeon's) judgment. The intensity of the bleeding at the TBS will
be rated by the investigator using the 5-point validated bleeding severity scale.
Exclusion Criteria:
Pre-operative:
1. Admitted for trauma surgery.
2. Unwilling to receive blood products.
3. Known history of severe (eg, anaphylactic) reaction to blood products.
4. Known history of intolerance to any of the components of the investigational product
(IP).
5. Female subjects who are pregnant, breastfeeding or, if of child-bearing potential (ie,
adolescent), unwilling to practice a highly effective method of contraception.
6. Previously enrolled in a clinical trial with FS Grifols.
7. Currently participating, or during the study is planned to participate, in any other
investigational device or medicinal product study without prior and explicit approval
from the sponsor.
Intra-operative:
8. An appropriate parenchymous or soft tissue TBS (as defined in exclusion criteria 9 and
10) cannot be identified intra-operatively by the investigator (the surgeon).
9. TBS has Grade 3 (severe) bleeding according to the investigator's (the surgeon's)
judgment that cannot be controlled with conventional surgical techniques to Grade 1 or
Grade 2 bleeding. The intensity of the bleeding at the TBS will be rated by the
investigator using the 5-point validated bleeding severity scale.
10. TBS is in an actively infected surgical field.
11. Occurrence of major intra-operative complications that require resuscitation or
deviation from the planned surgical procedure.
12. Application of any topical hemostatic agent on the resection surface of parenchyma or
soft tissue prior to application of the IP.
A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4)
This is a multicenter, open-label, phase 1, single arm study intended to determine the
optimal target dose and safety of bb2121 in subjects with HR (R-ISS Stage III per IMWG
criteria) NDMM. Subjects should have received 3 Cycles of standard induction therapy prior to
undergoing leukapheresis procedure to collect autologous mononuclear cells for manufacture of
the drug product (bb2121). Following manufacture of the drug product, subjects will receive
fourth cycle of induction therapy followed by lymphodepleting therapy with fludarabine and
cyclophosphamide prior to bb2121 infusion. Maintenance therapy is recommended for all
subjects who have received bb2121 infusion and should be initiated upon adequate bone marrow
recovery or from 90-day post-bb2121 infusion, whichever is later.
Subjects must satisfy all of the following criteria to be enrolled in the study:
1. Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to
initiating induction anti-myeloma therapy
2. Subject is ≥ 18 years of age at the time of initial diagnosis of MM
3. Subject has measurable disease at initial diagnosis by
• M-protein and/or
• Light chain MM without measurable disease in the serum or urine
4. Subject has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as
defined by IMWG:
• ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or
t(14:16) by iFISH; or;
• ISS Stage III and serum LDH > ULN
5. Subject has Eastern Cooperative Oncology Group performance ≤ 1
6. Subjects has received ≤ to 3 cycles of the following induction anti-myeloma therapy
prior to enrollment:
• Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd)
• Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone)
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment: The presence
of any of the following will exclude a subject from enrollment:
At initial diagnosis, screening and prior to initiation of induction therapy for MM:
1. Subject has non-secretory MM
During Screening:
2. Subject received any treatments for MM other than up to 3 cycles of induction therapy
per protocol
3. Subject has any of the following laboratory abnormalities:
1. Absolute neutrophil count < 1,000/μL
2. Platelet count < 50,000 mm3
3. Hemoglobin < 8 g/dL (< 4.9 mmol/L)
4. Serum creatinine clearance < 45 mL/min
5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
6. Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit
of normal
7. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented
Gilbert's syndrome
8. INR or aPTT > 1.5 × ULN
4. Subject has history or presence of clinically significant CNS pathology
5. Subjects has high risk for developing deep vein thrombosis or pulmonary embolus and
are unable or unwilling to undergo anti-thrombotic therapy
6. Subject has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE
Version 4.03 with bortezomib based induction regimen
7. Subjects has moderate or severe pulmonary hypertension
8. Subject has intolerance to components of induction regimen (KRd or RVd) or has any
contraindication to one or the other drug
9. Subject has not recovered from induction therapy-related toxicities (non-hematologic)
to < grade 1 CTCAE at the time of screening
10. Subject has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6
months of starting study treatment
11. Subject has cardiac conditions such as:
1. Echocardiogram or multi gated acquisition assessment of left ventricular ejection
fraction < 45%
2. Subject has a history of clinically significant cardiovascular disease or
clinically significant ECG abnormalities
12. Subject has Pulmonary conditions such as:
1. Subject has known chronic obstructive pulmonary with a forced expiratory vol in 1
sec 50% of predicted normal.
2. Inadequate pulmonary function defined as oxygen saturation < 92 % on room air
13. Subject needs ongoing treatment with chronic immunosuppressants
14. Subject has history of primary immunodeficiency
15. Subject is seropositive for human immunodeficiency virus, chronic or active hepatitis
B or active hepatitis A or C
First In Human (FIH) Study of REGN5459 in Patients With Relapsed or Refractory Multiple Myeloma (MM)
In the phase 1 portion of the study, the primary objectives are to assess the safety,
tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose
regimen (RP2DR) (defined as either a maximum tolerated dose regimen [MTDR] or biologically
effective dose regimen [BEDR]) of REGN5459 as monotherapy in patients with relapsed or
refractory multiple myeloma (MM) who have exhausted all therapeutic options that are expected
to provide meaningful clinical benefit. The determination of the RP2DR will be based on the
review of non-clinical and all clinical data, including that pertaining to safety,
pharmacokinetic (PK), PK/pharmacodynamics (PD) relationships, and efficacy.
In the phase 2 portion of the study, the primary objective is to assess the preliminary
anti-tumor activity of REGN5459 as measured by objective response rate (ORR).
In the phase 1 and phase 2 portion, the secondary objectives of the study are:
- To assess the preliminary anti-tumor activity of REGN5459 as measured by duration of
response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD)
negative status, and overall survival (OS)
- To evaluate the PK properties of REGN5459
- To characterize the immunogenicity of REGN5459 In the phase 1 portion of the study only,
the secondary objective of the study is to assess the preliminary anti-tumor activity of
REGN5459 as measured by ORR.
In the phase 2 portion of the study only, the secondary objective of the study is to evaluate
the safety and tolerability of REGN5459.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Individual cases of
patients with ECOG 2 performance status, whose ECOG status is expected to improve as a
consequence of effective therapy, may be discussed with the medical monitor for
potential enrollment
• Patients must have symptomatic myeloma at the time of study entry with myeloma-related
organ damage or tissue dysfunction (such as hypercalcemia, renal insufficiency, bone
lytic lesions, or anemia)
• Patients must have myeloma that is measurable by either serum or urine evaluation of
the monoclonal component or by assay of serum free light chain (FLC)
• Measurable disease is defined as 1 or more of the following:
1. Serum M-protein ≥1 g/dL,
2. Urine M-protein ≥200 mg/24-hour, and/or
3. FLC assay with involved FLC level ≥10 mg/dL with an abnormal serum FLC ratio
• A patient with Immunoglobulin A (IgA) myeloma but without measurable M-protein may be
enrolled if quantitative IgA levels are elevated and can be followed longitudinally
• A patient with non-secretory MM may be considered for enrollment after discussion with
the sponsor that includes the feasibility of an individualized plan for response
assessment
• Patients with MM who have exhausted all therapeutic options that are expected to
provide meaningful clinical benefit, either through disease relapse, treatment
refractory disease, or intolerance or refusal of the therapy, and including either:
1. Progression on or after at least 3 lines of therapy, or intolerance of therapy,
including a proteasome inhibitor, an IMiD, and an anti-CD38 antibody, OR
2. Progression on or after an anti-CD38 antibody and have disease that is "double
refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The
anti-CD38 antibody may have been administered alone or in combination with
another agent such as a proteasome inhibitor. Refractory disease is defined as
lack of response or relapse within 60 days of last treatment.
• Adequate hematologic function as measured by:
1. Platelet count > 50 x 109/L. A patient may not have received a platelet
transfusion within 7 days in order to meet this platelet eligibility requirement.
2. ANC > 1.0 x 109/L. A patient may not have received granulocyte colony stimulating
factor (G-CSF) within 2 days in order to meet this absolute neutrophil count
eligibility requirement.
3. Hemoglobin > 8.0 g/dL
• Adequate hepatic function, defined as:
1. Total bilirubin ≤1.5 x ULN
2. Transaminase (ALT, AST) ≤2.5 x ULN
3. Alkaline phosphatase ≤2.5 x ULN
• Patients with Gilbert syndrome do not need to meet this total bilirubin requirement
provided that the total bilirubin is unchanged from the baseline value.
d. Serum creatinine clearance by Cockcroft-Gault >30 mL/min
• A patient with a creatinine clearance by Cockcroft-Gault who does not meet eligibility
criteria may be considered for enrollment if a measured creatinine clearance (based on
24-hour urine collection or other reliable method) is >30 mL/min
• Life expectancy of at least 6 months
Key
Exclusion Criteria:
• Patients with known MM brain lesions or meningeal involvement with MM (suspected
central nervous system (CNS) myeloma should be excluded by radiographic imaging and/or
lumbar puncture, as appropriate)
• History of neurodegenerative condition or CNS movement disorder
• Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan
(MUGA)
• Prior treatment with any anti-BCMA antibody (including antibody-drug conjugate or
bispecific antibody) or BCMA-directed CAR T therapy
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus
(HBV) or hepatitis C virus (HCV) infection; or other uncontrolled infection
1. Patients with HIV who have controlled infection (undetectable viral load and CD4
count above 350 cells/microliter either spontaneously or on a stable antiviral
regimen) are permitted.
2. Patients with hepatitis B (Hepatitis B Surface Antigen Test positive [HepBsAg+])
who have controlled infection (serum HBV DNA polymerase chain reaction [PCR] that
is below the limit of detection AND receiving anti-viral therapy for hepatitis B)
are permitted.
3. Patients who are HCV antibody-positive (HCV Ab+) who have controlled infection
(undetectable HCV RNA by PCR either spontaneously or in response to a successful
prior course of anti-HCV therapy) are permitted.
• History of allogeneic stem cell transplantation at any time, or autologous stem cell
transplantation within 12 weeks of the start of study treatment
NOTE: Other protocol defined Inclusion/Exclusion Criteria apply.
Study to Evaluate Imetelstat (GRN163L) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion
dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is
relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment.
• Man or woman greater than or equal to (>=) 18 years of age
• In Part 1, diagnosis of myelodysplastic syndrome (MDS) according to World Health
Organization (WHO) criteria
• International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS
• Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units
transfused over an 8-week period during the 16 weeks prior to Study Entry;
pre-transfusion hemoglobin (Hb) should be less than or equal to 9.0 gram per deciliter
(g/dL) to count towards the 4 units total
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Exclusion Criteria:
• Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its
excipients
• Participant has received an investigational drug or used an invasive investigational
medical device within 30 days prior to Study Entry or is currently enrolled in an
investigational study
• Prior treatment with imetelstat
• Have received corticosteroids greater than (>) 30 milligram per day (mg/day)
prednisone or equivalent, or growth factor treatment within 4 weeks prior to study
entry
• a) Prior treatment with a hypomethylating agent (example [eg], azacitidine,
decitabine); b) Prior treatment with lenalidomide; c) Has received an
erythropoiesis-stimulating agent (ESA) or any chemotherapy, immunomodulatory, or
immunosuppressive therapy within 4 weeks prior to study entry (8 weeks for long-acting
ESAs)
Drug: Imetelstat, Drug: Placebo
Myelodysplastic Syndromes, Myeloid and Monocytic Leukemia
Myelodysplastic Syndromes, Imetelstat, GRN163L, Relapsed/refractory to ESAs, Transfusion dependent
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
A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer
This research study is done to test the safety of the new drug selitrectinib in children and
adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may
treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study
also investigates how the drug is absorbed and processed in the human body, and how well and
for how long the cancer responds to the drug. This is the first study to test selitrectinib
in humans with cancer, for whom no other effective therapy exists.
• Advanced solid tumor for which, in the opinion of the investigator, no other standard
therapy offers greater benefit.
• A solid tumor diagnosis in the setting of:
• a) a documented NTRK fusion and a clinical history of relapse following a
response to a prior TRK inhibitor
• b) a documented NTRK fusion unresponsive to a prior TRK inhibitor
• c) a documented NTRK fusion and a clinical history of intolerance to a prior TRK
inhibitor
• NTRK gene fusions will be identified in a CLIA-certified (or equivalently-accredited
diagnostic) laboratory. If such a report cannot be provided, other available
certifications/accreditations are required and need to be documented. Patients with
infantile fibrosarcoma (IFS) or congenital mesoblastic nephroma (CMN) may be enrolled
based on an ETV6+ FISH test without identifying NTRK3.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 2 in adults or
Karnofsky Performance Score (KPS) Score≥50% (age ≥ 16 years) or Lansky Performance
Score (LPS) ≥ 40% (age < 16 years).
• Life expectancy of at least 3 months.
• Adequate hematologic, hepatic and renal function.
• Patients with stable central nervous system (CNS) primary tumor, brain metastases, or
treated spinal cord compression are eligible if neurological symptoms have been stable
for 7 days prior to the first dose of selitrectinib.
• Ability to receive study drug orally or by enteral administration
Exclusion Criteria:
• Prior exposure to second generation TRK inhibitor (e.g. selitrectinib, repotrectinib
(TPX-0005)), taletrectinib (DS-6501b/AB-106)). Exception is in case patient presented
intolerance to the second generation TRK inhibitor agent and the duration of exposure
was less than 28 days. No previous treatment with selitrectinib is allowed.
• Concurrent treatment with a strong CYP3A4 inhibitor or inducer, consumption of
grapefruit juice or Seville oranges, or drugs associated with QT prolongation.
• Clinically significant active cardiovascular disease or history of myocardial
infarction within 3 months prior to planned start of selitrectinib, or prolongation of
QT interval corrected for heart rate (QTc interval) >480 milliseconds within past 6
months
• Major surgery within 7 days of enrollment
• Uncontrolled systemic bacterial, fungal or viral infection.
• Pregnancy or lactation.
• Known hypersensitivity to selitrectinib or Ora-Sweet® SF and OraPlus® for patients
receiving liquid formulation.
Drug: Selitrectinib (BAY2731954)
Multiple Myeloma, Mycosis Fungoides, Solid Tumors Harboring NTRK Fusion, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Kaposis sarcoma, Non-Hodgkins Lymphoma, Small Intestine, Soft Tissue
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
Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders
This is a randomized, controlled, open-label parallel arm study to assess the safety,
tolerability, pharmacokinetics and ammonia control, of RAVICTI® as compared to NaPBA in urea
cycle disorder subjects not currently or previously chronically treated with phenylacetic
acid (phenylacetate; PAA) prodrugs. The study design will include: 1) Baseline Period; 2)
Initial Treatment Period; 3) a RAVICTI only Transition Period 4) a RAVICTI only Maintenance
Period; and 5) a RAVICTI only Safety Extension Period. The study will run for approximately
25 weeks.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Markey McNutt
59152
All
up to 99 Years old
Phase 4
This study is NOT accepting healthy volunteers
NCT03335488
STU-2019-0706
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Signed informed consent given by the subject or the subject's parent/legal guardian
for those under 18 years of age or the age of consent by local regulation.
• Male and female subjects with a suspected or confirmed UCD diagnosis of any subtype,
except NAGS deficiency.
• Suspected diagnosis is defined as having experienced a HAC or a documented high
ammonia of >=100 µmol/L
• Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing.
• Requires nitrogen-binding agents according to the judgment of the Investigator
• Birth and older.
• All females of childbearing potential and all sexually active males must agree to
use an acceptable method of contraception from signing the informed consent
throughout the study and for 30 days after the last dose of study drug.
Acceptable forms of contraception are (oral, injected, implanted or transdermal),
tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier
methods. Abstinence is an acceptable form of birth control, though appropriate
contraception must be used if the subject becomes sexually active.
Exclusion Criteria:
• Subject has received chronic treatment with an oral phenylbutyrate (RAVICTI, NaPBA,
Pheburane, or other) longer than 14 consecutive days within one year prior to
enrollment.
• Temporary use of NaPBA for acute management of a hyperammonemic crisis in the past is
acceptable.
• Any concomitant illness (e.g., malabsorption or clinically significant liver or
bowel disease) which would preclude the subject's safe participation, as judged
by the Investigator.
• Has undergone liver transplantation, including hepatocellular transplant.
• Subjects on NaBz at Baseline will be excluded if they are viewed by the
Investigator as being unable to undergo NaBz transition to a PAA prodrug during
the Initial Treatment Period.
• Known hypersensitivity to PBA or any excipients of the NaPBA/PBA formulations.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a
pregnancy test performed at the Baseline Visit prior to the start of study drug.
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
To evaluate the clinical utility associated with the integration of Cxbladder into the
evaluation of subjects presenting with hematuria for evaluation of urothelial carcinoma (UC)
without compromising detection of UC.
Inclusion Criteria :
1. Patient is undergoing investigation of recent confirmed hematuria (by either flexible
or rigid cystoscopy/TURBT), including hematuria subjects referred due to
suspicious/positive imaging, in order to determine the presence of urothelial
carcinoma.
2. Able to provide a voided urine sample of the required minimum volume
3. Able to give written consent
4. Able and willing to comply with study requirements
5. Aged 18 years or older
Exclusion Criteria
1. Prior history of bladder malignancy, prostate or renal cell carcinoma
2. Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation,
urethral dilation) in the 14 days before urine collection,
3. History of glomerulonephritis, nephrosis or other renal inflammatory disorders, recent
history of pyelonephritis
4. Previous alkylating based chemotherapy
5. Pregnancy
An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)
This is an open-label, multicenter, dose confirmation, and PK study of JZP-458 in patients
(of any age) with ALL/LBL who are hypersensitive to E. coli-derived asparaginases (allergic
reaction or silent inactivation). This study is designed to assess the tolerability and
efficacy of JZP-458 (only in patients who develop hypersensitivity to an E. coli-derived
asparaginase), as measured by asparaginase activity.
1. Pediatric and adult patients with a diagnosis of ALL or LBL.
2. Have had an allergic reaction to a long-acting E. coli-derived asparaginase OR have
silent inactivation.
3. Have 1 or more courses of E. coli-derived asparaginase remaining in his/her treatment
plan.
4. Patients must have, in the opinion of the Investigator, fully recovered from their
prior allergic reaction to E. coli-derived asparaginase.
Exclusion Criteria:
1. Have previously received asparaginase Erwinia chrysanthemi or JZP-458.
2. Have relapsed ALL or LBL.
3. Are concurrently receiving another investigational agent and/or treated with an
investigational device at the same time as JZP-458 (within 48 hours) during Course 1
of JZP-458.
4. Have a history of ≥ Grade 3 pancreatitis.
5. Prior history of asparaginase-associated ≥ Grade 3 hemorrhagic event or
asparaginase-associated thrombus requiring anticoagulation therapy, excluding
catheter-related thrombotic events.
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).
A Phase 1 Trial of a Novel XPO1 Inhibitor in Patients With Advanced Solid Tumors
Study SL-801-0115 is a dose-escalation study evaluating multiple doses and schedules of
orally administered SL-801 in patients with Advanced Solid Tumors
• The patient must have histologic or cytologic evidence of a malignant solid tumor and
must have disease that is resistant to or relapsed following available standard
systemic therapy, or for which there is no standard systemic therapy or reasonable
therapy likely to result in clinical benefit.
• The patient must have advanced disease, defined as cancer that is either metastatic,
OR locally advanced and unresectable (and for which additional radiation therapy or
other locoregional therapies are not considered feasible).
• The patient must have disease that is measurable by standard imaging techniques, per
the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), or
evaluable per RECIST 1.1. (For patients with prior radiation therapy, measurable
lesions must be outside of any prior radiation field[s], unless disease progression
has been documented at that disease site subsequent to radiation.)
• The patient is ≥18 years old.
• The patient has an ECOG PS of 0-2.
• The patient has adequate baseline organ function, as demonstrated by the following:
• Serum creatinine ≤1.5 × institutional upper limit of normal (ULN) or calculated
creatinine clearance >30 mL/min.
• Serum albumin ≥2.5 g/dL.
• Bilirubin ≤1.5 × institutional ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ×
institutional ULN (patients with hepatic metastases must have AST/ALT ≤5 times
ULN).
• International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN;
and either partial thromboplastin time or activated partial thromboplastin time
(PTT or aPTT) ≤1.5 × ULN.
• The patient has adequate baseline hematologic function, as demonstrated by the
following:
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L
• Hemoglobin ≥8 g/dL, with no red blood cell (RBC) transfusions within the prior 14
days.
• Platelet count ≥100×10⁹/L, with no platelet transfusions within the prior 14
days.
• If the patient is a woman of child bearing potential (WOCBP), she has had a negative
serum or urine pregnancy test within 1 week prior to treatment.
• The patient (male and female) agrees to use acceptable contraceptive methods for the
duration of time on the study, and continue to use acceptable contraceptive methods
for 1 month after the last dose of SL-801.
• The patient has signed informed consent prior to initiation of any study-specific
procedures or treatment.
• The patient is able to adhere to the study visit schedule and other protocol
requirements, including follow-up for survival assessment.
Exclusion Criteria:
• The patient has persistent clinically significant ≥Grade 2 toxicities from previous
anticancer therapy (excluding Grade 2 chemotherapy-related neuropathy which is
permitted, and excluding Grade 2-3 laboratory abnormalities if they are not associated
with symptoms, are not considered clinically significant by the Investigator, and can
be managed with available medical therapies).
• The patient has received treatment with chemotherapy, external-beam radiation, or
other systemic anticancer therapy within 28 days prior to study entry (Patients with
advanced prostate cancer who are receiving luteinizing hormone releasing hormone
[LHRH] agonists are permitted onto the study and should continue use of these agents
during study treatment).
• The patient has received treatment with an investigational systemic anticancer agent
within 28 days prior to C1D1.
• The patient has previously received treatment with SL-801 or another investigational
agent that inhibits the XPO1/CRM1 pathway.
• The patient has an additional active malignancy that may confound the assessment of
the study endpoints. Patients with a past cancer history (active malignancy within 2
years prior to study entry) with substantial potential for recurrence must be
discussed with the Sponsor before study entry. Patients with the following concomitant
neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ
(including transitional cell carcinoma, cervical intraepithelial neoplasia),
organ-confined prostate cancer with no evidence of progressive disease.
• The patient has clinically significant cardiovascular disease (e.g., uncontrolled or
any New York Heart Association Class 3 or 4 congestive heart failure [Appendix 1],
uncontrolled angina, history of myocardial infarction, unstable angina or stroke
within 6 months prior to study entry, uncontrolled hypertension or clinically
significant arrhythmias not controlled by medication).
• The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic
obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's
opinion, would put the patient at significant risk for pulmonary complications during
the study.
• The patient has known active or suspected brain or leptomeningeal metastases. (Central
nervous system [CNS] imaging is not required prior to study entry unless there is a
clinical suspicion of CNS involvement). Patients with stable, treated brain metastases
are eligible provided there is no evidence of CNS disease growth on imaging for at
least 3 months following radiation therapy or other locoregional ablative therapy to
the CNS.
• The patient is receiving immunosuppressive therapy for prophylaxis following a prior
organ transplant (solid organ or allogeneic stem cell) or management of
immune-mediated toxicities due to immunotherapy. Low-dose corticosteroid (defined as <
10mg/day of prednisone or equivalent) therapy is permitted.
• The patient has uncontrolled intercurrent illness including, but not limited to,
uncontrolled infection, disseminated intravascular coagulation, or psychiatric
illness/social situations that would limit compliance with study requirements.
• The patient is pregnant or breast feeding.
• The patient has known positive status for human immunodeficiency virus active or
chronic Hepatitis B or Hepatitis C.
• The patient is oxygen-dependent.
• The patient has any medical condition which in the opinion of the Investigator places
the patient at an unacceptably high risk for toxicities.
Drug: SL-801
Lymphoma, Solid Tumors, Brain and Nervous System, Breast - Female, Breast - Male, Colon, Corpus Uteri, Esophagus, Kidney, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Other Digestive Organ, Pancreas, Prostate, Stomach, Urinary Bladder, Small Intestine, Unknown Sites
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
Lymphoma, 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)
• For patients who do not meet criteria for AML or MDS as outlined above; patient
has a history of transient myeloproliferative disorder (which may or may not have
required chemotherapy intervention and:
• Is > 8 weeks since resolution of transient myeloproliferative disease (TMD)
with >= 5% blasts, OR
• Has 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
Myelodysplastic Syndrome, Acute Myeloid Leukemia, Down Syndrome, Myeloid Leukemia Associated With Down Syndrome, Myeloproliferative Neoplasm, Myeloid and Monocytic Leukemia
A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent
chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the
study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy
regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the
recommended dose determined in Part 1.
• Eligible for study when participant is 1 year to 21 years at the time of diagnosis
• Eligible Ages in Australia and Canada; 2 years to 21 years
• De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present
at diagnosis:
• Age ≥ 10 years
• White blood cell (WBC) ≥ 50 × 10^3/μL
• CNS3 leukemia at diagnosis
• Systemic steroid pretreatment without presteroid WBC documentation
• Diagnostic bone marrow or peripheral blood sample must have gene expression profiling
and downstream genetic testing performed by submitting diagnostic specimens under the
COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or its successor study.
Specimens must demonstrate a Ph-like expression profile (ie, LDA-positive) as tested
by low density microarray testing at the COG ALL reference laboratory or TriCore
laboratory at the University of New Mexico AND must contain 1 of the following genetic
lesions: (determined at COG ALL reference laboratories, or equivalent
CAP/CLIA-certified laboratories approved by the medical monitor:
1. CRLF2 rearrangement* with confirmed JAK1 or JAK2 mutation (JAK+)
2. CRLF2 rearrangement* without JAK mutation
3. Other JAK pathway alterations (eg, JAK2 fusions, EPOR fusions, SH2B3 deletions,
IL7RA mutations) with or without CRLF2-R, or CRLF2-R with unknown JAK status*† as
determined by a COG ALL Reference Laboratory
• Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in
Study AALL1131 or its successor study, or as per the institutional standard of care
for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
• Male and female subjects of reproductive non childbearing potential or willing to take
appropriate precautions to avoid pregnancy or fathering a child for the duration of
study participation
Exclusion Criteria:
• Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception
of hydroxyurea or steroid pretreatment
• Trisomy 21 (Down syndrome)
• BCR-ABL1-rearranged (Ph+) ALL
• Calculated creatinine clearance or radioisotope glomerular filtration rate < 70
mL/min/1.73 m^2
• Alanine aminotransferase ≥ 5 × upper limit of normal (ULN) for age
• Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)
• History or evidence of cirrhosis
• Platelet count < 75 × 10^3/μL
• Absolute neutrophil count (ANC) < 750/μL
• Positive screen for hepatitis B or C
• Known human immunodeficiency virus infection
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/ Burkitt leukemia (BL), diffuse
large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), gray zone
lymphoma (GZL), and follicular lymphoma (FL) Note: Patients with B-cell NHL associated
with Nijmegen breakage syndrome will be allowed.
• Patients <25 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.
Patients with Burkitt leukemia who don't meet radiological criteria must have bone
marrow involvement of >25% by local assessment of bone marrow aspirate and/or biopsy.
• 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. Platelets ≥50000//mm3
3. 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.
• Clinically significant active infection confirmed by clinical evidence, imaging, or
positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.)
• Presence of active 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, Non-Hodgkins Lymphoma
Tisagenlecleucel, relapsed/refractory B-cell non-Hodgkin lymphoma, pediatric patients, Burkitt lymphoma (BL), Burkitt leukemia (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
A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant (AURIGA)
The purpose of this study is to evaluate conversion rate to minimal residual disease (MRD)
negativity following the addition of daratumumab to lenalidomide relative to lenalidomide
alone, when administered as maintenance treatment to anti-cluster of differentiation 38
(CD38) treatment naive participants with newly diagnosed multiple myeloma who are MRD
positive as determined by next generation sequencing (NGS) following high-dose therapy (HDT)
and autologous stem cell transplant (ASCT), with or without consolidation therapy.
• Have newly diagnosed multiple myeloma with a history of 4 to 8 total cycles of
induction with or without consolidation therapy and have received high-dose therapy
(HDT) and autologous stem cell transplantation (ASCT): (a) for participants who have
not received consolidation therapy, the participant must be within 180 days
post-transplant at the time of randomization; and (b) for participants treated with
consolidation therapy, the participant must be within 90 days of the last dose of
consolidation therapy at the time of randomization
• Must have a very good partial response (VGPR) or better response assessed per
International Myeloma Working Group (IMWG) 2016 criteria at the time of randomization
• Have archived bone marrow samples collected before induction treatment (that is, at
diagnosis) or before transplant (for example, at the end of induction) or have
existing results on the index multiple myeloma clone based on Adaptive
Biotechnologies' next generation sequencing (NGS)-based minimal residual disease (MRD)
assay. Archived bone marrow samples will be used for calibration of myeloma clonal
cells to facilitate assessment of primary end point by NGS. If an existing result on
index myeloma clone is available from Adaptive Biotechnologies' NGS-based MRD assay,
as part of institutional procedures, an archived bone marrow sample is not required as
long as Adaptive Biotechnologies is able to retrieve historical results on the index
myeloma clone form the clinical database. Any one of the following archived samples
are required: (a) Greater than 1 milliliter (mL) viable frozen bone marrow aspirated
aliquot (preferred) collected in an ethylenediaminetetra-acetic acid (EDTA) tube,
frozen, and stored at a temperature of -80 centigrade (°C), or; (b) Non-decalcified
diagnostic bone marrow aspirate clot sections (block or slides) for MRD assessment:
(i) A formalin fixed paraffin embedded (FFPE) block of bone marrow aspirate clot, or 5
slides, 5 micrometer each, of non-decalcified bone marrow, or (ii) 5 slides, bone
marrow aspirate smear
• Must have residual disease as defined by detectable MRD (Adaptive Biotechnologies' NGS
based MRD assay)
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0,
1, or 2
Exclusion Criteria:
• A history of malignancy (other than multiple myeloma) unless all treatment of that
malignancy was completed at least 2 years before consent and the participant has no
evidence of disease before the of date of randomization. Exceptions are squamous and
basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other
non-invasive lesion that in the opinion of the investigator, with concurrence with the
sponsor's medical monitor, is considered cured with minimal risk of recurrence within
3 years
• Have had prior treatment/therapy with: (a) Daratumumab or any other anti-cluster of
differentiation 38 (CD38) therapies, (b) Focal radiation therapy within 14 days prior
to randomization with the exception of palliative radiotherapy for symptomatic
management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14
days prior to randomization on measurable extramedullary plasmacytoma is not permitted
even in the setting of palliation for symptomatic management, or (c) Plasmapheresis
within 28 days of randomization
• Be exhibiting clinical signs of meningeal or central nervous system involvement due to
multiple myeloma
• Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory
volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
• Have known moderate or severe persistent asthma within the past 2 years or current
uncontrolled asthma of any classification
• Have any of the following: (a) Known history of seropositivity for human
immunodeficiency virus (HIV); (b) Seropositive for hepatitis B (defined by a positive
test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection
(that is, participants who are HBsAg negative but positive for antibodies to hepatitis
B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs])
must be screened using real-time polymerase chain reaction (PCR) measurement of
hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
EXCEPTION: Participants with serologic findings suggestive of HBV vaccination
(anti-HBs positivity as the only serologic marker) AND a known history of prior HBV
vaccination, do not need to be tested for HBV DNA by PCR; (c) Seropositive for
hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation
positive), except in the setting of a sustained virologic response, defined as
aviremia at least 12 weeks after completion of antiviral therapy)
Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage
Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with
AML relapsed/refractory after 2, 3, or 4 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, Venetoclax
Combination Regimens) 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 WHO
classification that has relapsed after, or is refractory to, two, three, or four 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 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.)
Patients with a history of IPSS-R high or very high risk MDS that transformed to AML
during treatment with hypomethylating drugs and then relapse following or are
refractory to a subsequent AML induction regimen may be enrolled as Second Salvage AML
patients. Additionally, patients with a history of MPN in accelerated phase (MPN-AP)
or high-risk primary myelofibrosis (PMF) that transformed to AML during treatment with
hypomethylating drugs and then relapse following or are refractory to a subsequent AML
induction regimen may be enrolled as Second Salvage AML patients.
2. Aged ≥ 18 years.
3. 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
the initiation of study treatment. At the investigator's discretion, for patients with
significant leukocytosis that develops 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. Inadequate Cardiac (left ventricular ejection fraction ≤40%) function.
4. White blood cell (WBC) count >15,000/μL (Note: Patients considered for possible
venetoclax-containing regimen must have WBC ≤10k/μL prior to initiating venetoclax
treatment).
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, active HBV or active HCV infection (note: testing for these
infections is not required). For patients with evidence of chronic hepatitis B virus
(HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if
indicated. Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load.
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, Kidney
Treatment of Hyperkalemia, Hyperkalemia, Potassium, Chronic Kidney Disease
A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma
Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part
B), First-in-Human (FIH) clinical study of CC-99712 in subjects with relapsed and refractory
multiple myeloma (MM). The dose escalation part (Part A) of the study will evaluate the
safety and tolerability of escalating doses of CC-99712, administered intravenously (IV), to
determine the maximum tolerated dose (MTD) and non-tolerated dose (NTD) of CC-99712 using a
modified accelerated titration design and Bayesian methodology. The MTD and NTD may be
established separately for CC-99712 administered at Q3W and/ or Q4W schedules. The expansion
part (Part B) will further evaluate the safety and efficacy of CC-99712 administered at or
below the MTD in selected expansion cohorts in order to determine the RP2D. One or more
dosing regimens may be selected for cohort expansion. All subjects will be treated until
confirmed disease progression per IMWG criteria, unacceptable toxicity, or
subject/Investigator decision to withdraw.
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject (male or female) is ≥ 18 years of age at the time of signing the ICF.
2. Subject has a history of MM with relapsed and refractory disease, and must:
• Have disease that is nonresponsive while on their last antimyeloma therapy or
documented disease progression on or within 60 days from the last dose of their
last antimyeloma therapy; and,
• Must have received at least 3 prior MM treatment regimens. and,
• Must have received a proteasome inhibitor, an immunomodulatory agent and an
anti-CD38 antibody (eg, daratumumab); and,
• Should have failed treatment with or are intolerant to all established therapies.
3. Subjects must have measurable disease, including at least one of the criteria below:
• M-protein quantities ≥ 0.5 g/dL by sPEP or
• ≥ 200 mg/24 hours urine collection by uPEP or
• Serum FLC levels > 100 mg/L (milligrams/liter involved light chain) and an
abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine
M-protein or
• For subjects with immunoglobulin class A (IgA) myeloma whose disease can only be
reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥
0.50 g/dL.
4. Subject has an ECOG PS of 0-1.
5. Subjects must have the following laboratory values (determined by local laboratory):
• Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
• Platelets (plt) ≥ 75 x 10^9/L.
• Potassium within normal limits or correctable with supplements.
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤
2.5 x upper limit of normal (ULN).
• Serum bilirubin ≤ 1.5 x ULN (or ≤ 2.0 x ULN for subjects with documented
Gilbert's syndrome).
• Estimated serum creatinine clearance of ≥ 60 mL/min
• International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time
(PTT) < 1.5 x ULN.
6. Females of childbearing potential (FCBP) must:
• Either commit to true abstinence from heterosexual contact (which must be
reviewed on a monthly basis and source documented) or agree to use, and be able
to comply with, at least two effective contraceptive methods (oral, injectable,
or implantable hormonal contraceptive; tubal ligation; intra-uterine device;
barrier contraceptive with spermicide; or vasectomized partner), one of which
must be barrier, from signing the ICF, throughout the study, during dose
interruptions, and for up to 42 days following the last dose of CC-99712; and
• Have two negative pregnancy tests as verified by the Investigator prior to
starting CC-99712. Subject must agree to ongoing pregnancy testing during the
course of the study, and after end of study treatment. This applies even if the
subject practices true abstinence from heterosexual contact. The subject may not
receive IP until the Investigator has verified that the result of the pregnancy
test is negative.
• a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at
Screening
• a negative serum or urine pregnancy test (Investigator's discretion) within
72 hours prior to Cycle 1 Day -1 of study treatment, and within 72 hours
prior to Day -1 of every subsequent cycle (note that the Screening serum
pregnancy test can be used as the test prior to Day -1 study treatment if it
is performed within the prior 72 hours). A serum or urine pregnancy test
(investigators discretion) must also be performed at the end of study for
each FCBP.
• Avoid conceiving for 42 days after the last dose of CC-99712.7. Males must
practice true abstinence (which must be reviewed on a monthly basis) or agree to
use a condom (a latex condom is recommended) during sexual contact with a
pregnant female or a FCBP and will avoid conceiving from signing the ICF, while
participating in the study, during dose interruptions, and for at least 42 days
following CC-99712 discontinuation, even if he has undergone a successful
vasectomy.
8. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. In Part A only, subject has received prior investigational therapy directed at BCMA.
2. Subject has symptomatic central nervous system involvement of MM.
3. Subject has nonsecretory MM, plasma cell leukemia, Waldenstrom's macroglobulinemia,
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes), or amyloidosis.
4. Subjects with a history of class III or IV congestive heart failure (CHF) or severe
non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular
arrhythmia within the previous 6 months prior to signing ICF.
5. Subject had a prior autologous stem cell transplant ≤ 3 months prior to starting
CC-99712.
6. Subject had a prior allogeneic stem cell transplant with either standard or reduced
intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic
immunosuppression for graft-versus host disease.
7. Subject had a prior chimeric antigen receptor T (CAR T) cell product ≤ 4 weeks prior
to starting CC-99712.
8. Subject had a prior systemic cancer-directed treatments or investigational modalities
within 5 pharmacokinetic half-lives or 2 weeks prior to starting CC-99712, whichever
is longer. The only exception is emergency use of a short course of corticosteroids
(equivalent of dexamethasone 40 mg/day for a maximum 4 days) before treatment.
9. Subject had major surgery ≤ 2 weeks prior to starting CC-99712. Subjects must have
recovered from any clinically significant effects of recent surgery.
10. Subject is a pregnant or lactating female.
11. Subject has known human immunodeficiency virus (HIV) infection.
12. Subject has known history of chronic, active hepatitis B or C virus (HBV/HCV)
infection.
13. Subject requires ongoing treatment with chronic, therapeutic dosing of anti-coagulants
(eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
14. Subject has a history of concurrent second cancers requiring active, ongoing systemic
treatment.
15. Subject has known history of cirrhosis or has clinically significant liver or biliary
disease. Subjects with stable chronic liver or biliary disease (such as Gilbert's
syndrome, asymptomatic gallstones, or hepatobiliary involvement of malignancy) may
participate in the study, however, sponsor medical monitor must be contacted for a
discussion before enrollment.
16. Subject has a history of clinically significant corneal disease requiring therapy or
ongoing active corneal disease.
17. Subject has active peripheral neuropathy or neuropathic pain Grade 2 or higher, as
defined by the National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE v5.0).
Drug: CC-99712
Multiple Myeloma
Multiple Myeloma, Relapsed and refractory, CC-99712, BCMA, Antibody drug conjugate
An Open-Label, Multicenter, Extension Study for Subjects Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose)
Extension study for subjects who participated in a previous Astex-sponsored clinical study of
ASTX727 (including, but not limited to ASTX727-01, ASTX727-02, ASTX727-04).
Subjects must fulfill all of the following inclusion criteria:
1. Previous participation in an Astex-sponsored ASTX727 clinical trial (including, but
not limited to studies ASTX727-01, ASTX727-02, and ASTX727-04) in which the subject
was treated with ASTX727 and was still on active treatment with ASTX727 at the time of
study completion as determined by Astex.
2. Subject is considered to be benefitting from ASTX727 treatment in the opinion of the
treating investigator at the time of parent study completion (Subjects must not be
withdrawn from the parent study until eligibility for this study is confirmed).
3. Subject is able to understand and comply with the study procedures and understands the
risks involved in the study.
4. Subject provides written informed consent before undergoing any study-specific
procedure.
5. Women of childbearing potential must not be pregnant or breastfeeding and must have a
negative pregnancy test at screening. Women of childbearing potential must agree to
practice 2 highly effective contraceptive methods of birth control and must agree not
to become pregnant for 6 months after completing treatment; men with female partners
of childbearing potential must agree to practice 2 highly effective contraceptive
measures and must agree not to father a child while receiving ASTX727 and for at least
3 months after completing ASTX727 treatment.
Exclusion Criterion:
1. Any subject who, in the opinion of the investigator, may have other conditions, organ
dysfunction, or for whom safety data from parent study participation suggests the risks of
continuing treatment with ASTX727 may outweigh the benefits.