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.
Phase 1 Study of MM-398 Plus Cyclophosphamide in Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The
goal is to find the highest dose of MM-398 that can be given safely when it is used together
with the chemotherapy drug Cyclophosphamide.
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma,
neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid
Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of
a patient <18 years of age will provide informed consent and patients 11 to 18 years
of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled
blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for
pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Neuroblastoma, Sarcoma, Ewing Sarcoma, Mycosis Fungoides, Rhabdomyosarcoma, Osteosarcoma, Recurrent or Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, 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, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Kaposis sarcoma, Other Hematopoietic, Small Intestine, Soft Tissue
Efficacy and Safety of Viaskin Milk in Children With IgE-Mediated Cow's Milk Allergy (MILES)
The objectives of this study are to evaluate the safety and efficacy of Viaskin Milk after 12
months of epicutaneous immunotherapy (EPIT) treatment, for desensitizing IgE-mediated cow's
milk allergic children and to assess the long-term safety and therapeutic benefit with
Viaskin Milk.
Call 214-648-5005 studyfinder@utsouthwestern.edu
John Bird
108478
All
2 Years to 17 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT02223182
STU 092014-046
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Eligibility criteria for study enrollment:
Inclusion Criteria:
• Signed Informed Consent Form (ICF) by parent(s)/guardian(s) of subjects and informed
assent form (IAF) for subjects ≥7 years, or as per local or country specific
guidelines or regulations.
• Male or female subjects 2 to 17 years old at Visit 1.
• Documented medical history or physician-confirmed diagnosis of IgE-mediated CMA with
systemic symptoms related to ingestion of milk or dairy products.
• Subjects currently following a strict cow's milk-free diet, with no consumption of
dairy or baked milk products.
• Cow's milk-specific IgE level at screening ≥10 kU/L
• Positive Skin Prick Test (SPT) to cow's milk with a largest wheal diameter ≥6 mm.
• Positive DBPCFC at screening with an eliciting dose ≤300 mg cow's milk proteins
(approximately ≤9.4 mL of cow's milk).
• Negative urine pregnancy test for female subjects of childbearing potential. Female
subjects of childbearing potential must agree and commit to use effective medical
methods of contraception for the entire duration of their participation in the study.
Sexual abstinence will be accepted as an effective method of contraception for girls
below 15 years of age.
• Ability to perform spirometry procedures in accordance with the American Thoracic
Society guidelines (2005) for subjects ≥6 years old. Ability to perform peak
expiratory flow (PEF) measurements for subjects ≥5 years old. Subjects <8 years of age
who have documented inability to adequately perform spirometry can perform only the
PEF evaluation. Subjects <5 years of age may be enrolled if they had no clinical
features of moderate or severe persistent asthma severity (as defined by the 2007
National Heart, Lung, and Blood Institute [NHLBI] Guidelines) within 1 year before
Visit 1.
• Subjects and/or parents/guardians willing to comply with all study requirements during
participation in the study.
Exclusion Criteria:
• History of severe anaphylaxis to cow's milk resulting in hypotension, hypoxia or
neurological compromise (collapse, loss of consciousness or incontinence) or requiring
mechanical ventilation.
• Pregnancy or lactation.
• Spirometry forced expiratory volume in 1 second (FEV1) <80% of the predicted value at
Visit 1 for subjects ≥6 years and able to perform the spirometry, or PEF <80% of
predicted value at Visit 1 for subjects performing only the PEF measurements.
• Any clinical features of moderate or severe persistent asthma severity (as defined by
the 2007 NHLBI guidelines) and high daily doses of inhaled corticosteroids.
• Known allergy to the Viaskin patch materials or excipients, or to any of the
components of the food challenge formulas other than the cow's milk proteins.
• Allergy or known history of reaction to Tegaderm® medical dressing with no possibility
to use an alternative adhesive dressing authorized by the sponsor in replacement.
• Subjects having objective symptoms to the placebo formula leading to stopping the
challenge during the screening DBPCFC.
• Severe reaction during the screening DBPCFC defined as need for intubation, and/or
hypotension persisting after epinephrine administration, and/or the need for >2 doses
of epinephrine.
• Symptomatic allergy to pollens with symptoms during the pollen season that might
interfere with the symptoms observed during the DBPCFC, if the DBPCFC is performed
during the pollen season. Screening of such subjects should be made out of the pollen
season.
• Inability to discontinue short-acting antihistamines for 3 days or long-acting
antihistamines for 5 to 7 days (depending on the half-life) before the DBPCFC.
• Use of systemic long-acting corticosteroids within 12 weeks before Visit 1 and/or use
of systemic short-acting corticosteroids within 4 weeks before Visit 1 or use of
systemic long-acting or short-acting corticosteroids during screening (unless used to
treat symptoms triggered by the DBPCFC or triggered by accidental allergen
consumption; in the latter case DBPCFC must then be scheduled after a minimum of 7
wash-out days).
• Subjects with asthma conditions meeting 1 or several criteria below:
• Uncontrolled persistent asthma (as defined by the 2007 NHLBI guidelines) or
subject being treated with a combination therapy of medium or high daily dose of
inhaled corticosteroid with a long acting inhaled β2-agonist. Intermittent
asthmatic subjects who require intermittent use of inhaled corticosteroids for
rescue are permitted.
• At least 2 systemic corticosteroid courses for asthma within 1 year before Visit
1 or 1 oral corticosteroid course for asthma within 3 months before Visit 1, or
during screening (unless used to treat symptoms triggered by the DBPCFC).
• Prior intubation/mechanical ventilation due to asthma within 2 years before Visit
1, or during screening.
• Upper respiratory infection or gastroenteritis within 7 days of DBPCFC (DBPCFC must
then be rescheduled at least 7 days after resolution of these conditions).
• Any history of milk immunotherapy (eg, oral immunotherapy, sublingual immunotherapy or
specific oral tolerance induction).
• Prior history of any other food allergen immunotherapy (eg, oral immunotherapy,
sublingual immunotherapy or specific oral tolerance induction) within 5 years before
Visit 1.
• Subjects currently under aeroallergen immunotherapy and unwilling or unable to
discontinue at the time of Visit 1. Aeroallergen Immunotherapy must be discontinued at
the time of Visit 1.
• Use of any anti-IgE drug (eg, omalizumab), any immunomodulatory therapy, or any
biological agent therapy (eg, anti-tumor necrosis factor drugs) within 1 year before
Visit 1, or during screening.
• Generalized dermatologic diseases (eg, severe atopic dermatitis, uncontrolled
generalized eczema, icthyosis vulgaris) with no intact zones to apply the Viaskin
patch, or urticarial and mast cells disorders such as chronic idiopathic urticaria.
• Subject and/or subject's parents/guardians with obvious excessive anxiety and unlikely
to cope with the conditions of a food challenge.
• Past or current disease, including but not limited to active eosinophilic
gastrointestinal disorders, autoimmune disorders, immunodeficiency, malignancy,
uncontrolled disease (hypertension, diabetes, psychiatric disorder, cardiac disease),
or other disorders (eg, liver, gastrointestinal, kidney, cardiovascular, pulmonary
disease or blood disorder) which in the opinion of the Investigator or the sponsor may
affect the subject's participation in the study or place the subject at increased
risk.
• Subjects and/or parents/guardians unable to use the epinephrine auto-injector properly
in spite of being adequately trained.
• Contraindicated condition for the use of epinephrine.
• Use of any investigational drug or device, or participation in another interventional
clinical study within 3 months before Visit 1.
• Subjects receiving beta-blockers or Angiotensin converting-enzyme (ACE) inhibitors.
• Subjects unable to follow the protocol requirements.
Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)
The main objective of this study is to evaluate the efficacy of SRP-4045 and SRP-4053
compared to placebo in Duchenne muscular dystrophy (DMD) patients with out-of-frame deletion
mutations amenable to skipping exon 45 and exon 53, respectively.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Susan Iannaccone
13463
Male
7 Years to 13 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT02500381
STU 082015-050
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Inclusion Criteria:
• Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53
skipping
• Stable dose of oral corticosteroids for at least 24 weeks
• Intact right and left biceps or 2 alternative upper muscle groups
• Mean 6MWT greater than or equal 300 meters and less than or equal to 450 meters
• Stable pulmonary function: forced vital capacity (FVC) equal to or greater than 50%
predicted
Exclusion Criteria:
• Treatment with gene therapy at any time
• Previous treatment with SMT C1100, PRO045 (BMN 045), PRO053 (BMN 053) or PRO051 (BMN
051) within 24 weeks prior to Week 1
• Current or previous treatment with any other experimental treatment (other than
deflazacort) within 12 weeks prior to Week 1
• Major surgery within 3 months prior to Week 1
• Presence of other clinically significant illness
Other inclusion/exclusion criteria may apply
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
This randomized phase III trial studies how well combination chemotherapy (vincristine
sulfate, dactinomycin, cyclophosphamide alternated with vincristine sulfate and irinotecan
hydrochloride or vinorelbine) works compared to combination chemotherapy plus temsirolimus in
treating patients with rhabdomyosarcoma (cancer that forms in the soft tissues, such as
muscle), and has an intermediate chance of coming back after treatment (intermediate risk).
Drugs used work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Combination
chemotherapy and temsirolimus may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth. It is not yet known whether chemotherapy plus temsirolimus is
more effective than chemotherapy alone in treating patients with intermediate-risk
rhabdomyosarcoma.
• Feasibility Phase: Patients must be < 21 years of age at the time of enrollment;
please note: the feasibility phase is complete, effective with amendment #1
• Efficacy Phase: Patients must be =< 40 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based
upon institutional histopathologic classification, are eligible to enroll on the study
based upon stage, group, and age, as below
• RMS types included under embryonal rhabdomyosarcoma (ERMS) include those classified in
the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic,
spindle cell, and botryoid variants), which are reclassified in the 2013 World Health
Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and
spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and
the newly recognized sclerosing RMS variant); classification of alveolar
rhabdomyosarcoma (ARMS) in the 2013 WHO classification is the same as in the ICR and
includes classic and solid variants
• ERMS
• Stage 1, group III (non-orbit)
• Stage 3, group I/II
• Stage 2/3, group III
• Stage 4, group IV, < 10 years old
• ARMS:
• Stages 1-3, groups I-III
• Specimen Submission: Patients must have sufficient tissue available for the required
biology study
• Lansky performance status score >= 50 for patients =< 16 years of age; Karnofsky
performance status score >= 50 for patients > 16 years of age
• Peripheral absolute neutrophil count (ANC) >= 750/uL
• Platelet count >= 75,000/uL
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• 1 month to < 6 months old: 0.4 mg/dl (male), 0.4 mg/dl (female)
• 6 months to < 1 year old: 0.5 mg/dl (male), 0.5 mg/dl (female)
• 1 to < 2 years old: 0.6 mg/dl (male), 0.6 mg/dl (female)
• 2 to < 6 years old: 0.8 mg/dl (male), 0.8 mg/dl (female)
• 6 to < 10 years old: 1 mg/dl (male), 1 mg/dl (female)
• 10 to < 13 years old: 1.2 mg/dl (male), 1.2 mg/dl (female)
• 13 to < 16 years old: 1.5 mg/dl (male), 1.4 mg/dl (female)
• >= 16 years old: 1.7 mg/dl (male), 1.4 mg/dl (female)
• Patients with an elevated serum creatinine due to obstructive hydronephrosis
secondary to tumor are still eligible; however, patients with urinary tract
obstruction by tumor must have unimpeded urinary flow established via diversion
(i.e. percutaneous nephrostomies or ureteric stents) of the urinary tract
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• 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 who have previously received temsirolimus, another mTOR inhibitor, or any
other investigational agent
• Patients who have received any chemotherapy (excluding steroids) and/or RT prior to
this enrollment
• Patients with uncontrolled hyperglycemia
• Patients with uncontrolled hyperlipidemia
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
at least 3 months after treatment is completed
• Female patients who are pregnant are not eligible since fetal toxicities or
teratogenic effects have been noted for several of the study drugs; Note: A pregnancy
test is required for female patients of childbearing potential prior to study entry
• Lactating females who plan to breastfeed their infants are not eligible
Study to Assess Safety and Preliminary Activity of Eribulin Mesylate in Pediatric Participants With Relapsed/Refractory Rhabdomyosarcoma (RMS), Non-rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) and Ewing Sarcoma (EWS)
This study will be conducted as an assessment of the safety and preliminary activity of
eribulin mesylate in pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS),
non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), or Ewing sarcoma (EWS) to determine whether
each cohort warrants further investigation.
• Age: ≥12 months to <18 years old at the time of informed consent
• Diagnosis: Histologically confirmed rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft
tissue sarcoma (NRSTS) (Grade 2 or 3), or Ewing sarcoma (EWS) which is relapsed or
refractory (failed front line therapy)
• The presence of measurable disease meeting the following criteria:
• At least 1 lesion of ≥1.0 centimeter (cm) in the longest diameter for a non-lymph
node or ≥1.5 cm in the short-axis diameter for a lymph node that is serially
measurable according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
using computerized tomography/magnetic resonance imaging (CT/MRI).
• Lesions that have had radiotherapy must show subsequent radiographic evidence of
increase in size by at least 20% to be deemed a target lesion.
• Therapeutic options: Participant's current disease state must be one for which there
is no known curative therapy or therapy proven to prolong survival with an acceptable
quality of life.
• Performance level: Performance score ≥50%. Karnofsky (for participants >16 years of
age) or Lansky (for participants ≤16 years of age). Participants who are unable to
walk because of paralysis and/or previous surgeries, but who are in a wheelchair, will
be considered ambulatory for the purpose of assessing performance score.
• Participants must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior anticancer
directed therapy prior to study drug administration. If, after the required time
frame, the numerical eligibility criteria are met, eg, blood count criteria, the
participant is considered to have recovered adequately:
• Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21
days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days
if prior nitrosourea).
• Anticancer agents not known to be myelosuppressive (eg, not associated with
reduced platelet or absolute neutrophil count [ANC] counts): ≥7 days after the
last dose of agent.
• Monoclonal antibodies ≥ 3 half-lives must have elapsed from infusion of last dose
of antibody (including checkpoint inhibitors), and toxicity related to prior
antibody therapy must be recovered to Grade ≤1.
• Hematopoietic growth factors: ≥14 days after the last dose of a long-acting
growth factor (eg, Neulasta) or 7 days for a short-acting growth factor. For
agents that have known adverse events (AEs) occurring beyond 7 days after
administration, this period must be extended beyond the time during which AEs are
known to occur. The duration of this interval must be discussed with the sponsor.
• Interleukins, interferons, and cytokines (other than hematopoietic growth
factors): ≥21 days after the completion of interleukins, interferons, or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]): ≥84 days
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell
infusion including donor lymphocyte infusion or boost infusion: ≥84 days after
infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: ≥42 days
• Cellular therapy: ≥42 days after the completion of any type of cellular therapy
(eg, modified T-cells, natural killer cells, dendritic cells, etc)
• Radiation therapy (XRT)/External Beam Irradiation including Protons: ≥14 days
after local XRT; ≥150 days after TBI, craniospinal XRT or if radiation to ≥50% of
the pelvis; ≥42 days if other substantial BM radiation
• Radiopharmaceutical therapy (eg, radiolabeled antibody,
131I-metaiodobenzylguanidine): ≥42 days after systemically administered
radiopharmaceutical therapy.
• Adequate bone marrow function, defined as:
• ANC ≥1.0 × 10^9/Liter (L)
• Platelet count ≥100 × 10^9/L (transfusion independent, defined as not receiving
platelet transfusions within a 7-day period prior to study drug administration)
• Hemoglobin at least 8.0 grams per deciliter (g/dL) at Baseline (blood
transfusions are allowed during the screening period to correct hemoglobin values
less than 8.0 g/dL) Note: As blood transfusions are permitted to meet the
hemoglobin criteria, participants requiring transfusion must not be known to be
refractory to red blood cell or platelet transfusions.
• Adequate renal function, defined as:
• A serum creatinine based on age/gender, derived from the Schwartz formula for
estimating glomerular filtration rate (GFR)
• Or creatinine clearance or GFR ≥50 milliliters per minute (mL/min)/1.73 meters
squared (m^2) based on a 12 or 24 hour urine creatinine collection
• Adequate liver function, defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤1.5 × upper limit of normal (ULN)
for age
• Alanine aminotransferase (ALT) ≤110 units per Liter (U/L). For the purpose of
this study, the ULN for ALT is 45 U/L
• Serum albumin ≥2 g/dL
• Informed consent: All participants and/or their parents or legally authorized
representatives must sign a written informed consent. Assent, when appropriate, will
be obtained according to institutional guidelines. Participants must be willing to
comply with all aspects of the protocol.
Exclusion Criteria:
• Pregnancy, breastfeeding, contraception: Females who are breastfeeding or pregnant at
Screening or Baseline (as documented by a positive beta-human chorionic [β-hCG] or
human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 International
Units per Liter [IU/L] or equivalent units of β-hCG [or hCG]). A separate baseline
assessment is required if a negative screening pregnancy test was obtained more than
72 hours before the first dose of study drug.
• Females of childbearing potential (all post pubertal females will be considered
to be of childbearing potential unless they have early menopause [amenorrheic for
at least 12 consecutive months, in the appropriate age group, and without other
known or suspected cause] or have been sterilized surgically [ie, bilateral tubal
ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at
least 1 month before dosing]) who:
• Do not agree to use a highly effective method of contraception for the entire
study period and for 6 months after study drug discontinuation, ie:
• Total abstinence (if it is their preferred and usual lifestyle);
• An intrauterine device (IUD) or intrauterine system (IUS);
• A contraceptive implant;
• An oral contraceptive (must be on a stable dose of the same oral hormonal
contraceptive product for at least 4 weeks before dosing with study drug and for
the duration of the study and for 6 months after study drug discontinuation); or
• Do not have a vasectomized partner with confirmed azoospermia.
For sites outside of the European Union (EU), it is permissible that if a highly effective
method of contraception is not appropriate or acceptable to the participant, or the
participant has commenced/adjusted/changed oral hormonal contraceptive product/dose within
4 weeks prior to study drug administration, then the participant must agree to use a
medically acceptable method of contraception, ie, double barrier methods of contraception
such as condoms plus diaphragm or cervical/vault cap with spermicide.
• Males who have not had a successful vasectomy (confirmed azoospermia) or if they and
their female partners do not meet the criteria above (ie, not of childbearing
potential or practicing highly effective contraception throughout the study period or
for 3 months after study drug discontinuation). No sperm donation is allowed during
the study period or for 3 months after study drug discontinuation.
•Concomitant medications:
• Corticosteroids: Participants receiving corticosteroids who have not been on a stable
or decreasing dose of corticosteroid for at least 7 days prior to study drug
administration (except when indicated for Central Nervous System [CNS] metastases,
then participants must not have received corticosteroids for at least 28 days)
• Anticancer Agents: participants who are currently receiving other anticancer agents
• Anti-GVHD agents Post-transplant: Participants who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant
• Strong CYP3A4 inducers/inhibitors
• Received prior therapy with eribulin mesylate
• Any other malignancy that required treatment (except for non-melanoma skin
cancer, or histologically confirmed complete excision of carcinoma in situ),
within 2 years prior to study drug administration
• Has hypersensitivity to eribulin or any of the excipients
• Has a prior history of viral hepatitis (B or C) as demonstrated by positive
serology (presence of antigens) or have an uncontrolled infection requiring
treatment. Participants with a known prior history of hepatitis B or C may be
eligible pending agreement with the sponsor.
• Has > Grade 1 peripheral sensory neuropathy or > Grade 1 peripheral motor
neuropathy graded according to the Modified ("Balis") Pediatric Scale of
Peripheral Neuropathies
• Has cardiac pathology: Participants with known congestive heart failure,
symptomatic or left ventricular (LV) ejection fraction <50% or shortening
fraction <27%
• Participants with congenital long QT syndrome, bradyarrhythmias, or QTc >480 msec
on at least 2 separate electrocardiograms (ECGs).
• Has CNS Disease: Participants with brain or subdural metastases are not eligible
unless the metastases are asymptomatic and do not require treatment or have been
adequately treated by local therapy (eg, surgery or radiotherapy) and have
discontinued the use of corticosteroids for this indication for at least 4 weeks
prior to study drug administration. Confirmation of radiographic stability must
be done by comparing the brain scan (CT or MRI) performed during the Screening
Period, using the same imaging modality, to a brain scan performed earlier (and
following local therapy where applicable). Participants must be clinically
stable. It is not the intention of this protocol to treat participants with
active brain metastases.
Note: CNS imaging is required to confirm eligibility for participants with a known history
of CNS disease.
• Have had or are planning to have the following invasive procedures:
• Major surgical procedure or significant traumatic injury within 28 days prior to
study drug administration
• Laparoscopic procedure or open biopsy within 7 days prior to study drug
administration
• Central line placement or subcutaneous port placement is not considered major
surgery but must be placed at least 2 days prior to study drug administration
• Core biopsy, including bone marrow biopsy, within 2 days prior to study drug
administration
• Fine needle aspirate within 3 days prior to study drug administration
• Has any serious concomitant illness that in the opinion of the investigator(s) could
affect the participant's safety or interfere with the study assessments
• Participants with known human immunodeficiency virus (HIV); due to lack of available
safety data for eribulin therapy in HIV-infected participants
1. Subjects with a diagnosis of iobenguane avid, relapsed, high-risk neuroblastoma based
on revised INRC criteria who have completed at least one cycle of induction and
consolidation therapy with an INRC criterion of partial response or better, and then
showed new progressive disease (revised INRC criteria progressive disease) as
described in Park, et al. (2017).This may include one or more of the following drugs:
cyclophosphamide or ifosfamide, cisplatin or carboplatin, vincristine, doxorubicin
(adriamycin), etoposide, topotecan, and/or busulfan and melphalan (sometimes used
during stem cell transplant) and/or immunotherapy. (If a subject is symptomatic and
for logistical reasons cannot be treated immediately with 131I-MIBG, 1 to 2 cycles of
"bridging chemotherapy" or immunotherapy will be permitted. If "bridging chemotherapy"
or immunotherapy is applied, approximately 4 weeks will be required for reassessment
of the baseline including tumor assessment.
2. Must be therapeutic 131I-MIBG naive.
3. All soft tissue lesions identified on CT/MRI scans must be iobenguane-avid lesions on
an iobenguane (123I) scan or any non iobenguane avid lesions biopsy proven to be
non-tumor lesions.
4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least
2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
5. If a man, must agree to use an adequate contraception method as deemed appropriate by
the Investigator (e.g., vasectomy, condoms) or partner using effective contraception
and to not donate sperm during the study and for 90 days after receiving the last dose
of study drug.
6. If a woman of childbearing potential, have a negative serum pregnancy test result
prior to each dosing and, if sexually active, be practicing an effective method of
birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a
cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner
sterilization throughout the study.
7. Age at study entry ≥1 year.
8. Previous platelet transfusions are permitted, as long as the subject has a platelet
count ≥50,000/μL without transfusion support for at least 1 week.
9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
10. An absolute neutrophil count ≥750/μL without growth factor for 5 days.
11. Liver function parameter results: total bilirubin ≤1.5 × upper limit of normal for
age, and serum glutamic-pyruvic transaminase (alanine aminotransferase) [SGPT (ALT)]
and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) [SGOT (AST)]
<3 × upper limit of normal (note that for ALT, the upper limit of normal for all sites
is defined as 45 U/L).
12. Normal thyroid function as measured by T4 and TSH or have abnormal results that are
not considered clinically important by the Investigator or may be receiving
levothyroxine.
13. Cardiac Function: Ejection fraction (≥55%) documented by echocardiogram within 1 month
prior to Visit 1 (baseline).
14. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance
Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
15. Full recovery from the toxic effects of any prior therapy.
Exclusion Criteria:
1. Evidence of non-avid iobenguane lesions on iobenguane (123I) scan including soft
tissue disease on CT/MRI that is not iobenguane-avid.
2. Subjects with primary refractory disease.
3. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not
recovered from effects of any biologic therapy.
4. Subjects that are refractory to the prior treatment regimen.
5. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
6. Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit
1 are excluded. Those who have received allogeneic stem cell treatment more than 4
months from Visit 1 must have recovered and have no active graft versus host disease
(GVHD) to be eligible.
7. History of local radiation therapy within the last 3 months.
8. History of total body irradiation.
9. Subjects do not have adequate renal function defined as adjusted serum creatinine ≥1.5
× upper limit of normal for sex and age.
10. Subjects who are on hemodialysis.
11. Pregnancy or breastfeeding.
12. Significant active infections including active hepatitis B, or hepatitis C infection,
or known infection with human immunodeficiency virus (HIV) (testing for HIV is not
required prior to study entry).
13. Clinically important cardiac, pulmonary, and hepatic impairment.
Drug: 131I-MIBG
Neuroblastoma, Neoplasms, Neuroectodermal Tumors, Brain and Nervous System
Study of Intrathecal Administration of Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy (STRONG)
The purpose of this trial is to evaluate the safety and tolerability of intrathecal
administration of onasemnogene abeparvovec-xioi in infants and children with Spinal Muscular
Atrophy with 3 copies of SMN2 and deletion of SMN1.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Susan Iannaccone
13463
All
6 Months to 60 Months old
Phase 1
This study is NOT accepting healthy volunteers
NCT03381729
STU 062016-082
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Key Inclusion Criteria
• Patients ≥6 months and up to 60 months (1800 days) of age at time of dosing following
diagnostic confirmation during screening period by genotype who demonstrate the
ability to sit unassisted for 10 or more seconds but cannot stand or walk
• Diagnostic confirmation by genotype includes lab documentation of homozygous absence
of SMN1 exon 7; with exactly three copies of SMN2
• Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
• Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) at
< 12 months of age
• Able to sit independently and not standing or walking independently. Definition of
sitting independently is defined by the World Health Organization Multicentre Growth
Reference Study (WHO-MGRS) criteria of being able to sit up unsupported with head
erect for at least 10 seconds. Child should not use arms or hands to balance body or
support position (Wijnhoven 2004)
• Be up-to-date on childhood vaccines that include palivizumab prophylaxis (also known
as Synagis) to prevent respiratory syncytial virus (RSV) infections are also
recommended in accordance with American Academy of Pediatrics (AAP 2009)
Key Exclusion Criteria
• Current or historical ability to stand or walk independently
• Contraindications for spinal tap procedure or administration of intrathecal therapy or
presence of an implanted shunt for the drainage of CSF or an implanted central venous
(CNS) catheter
• Severe contractures as determined by designated Physical Therapist(s) at screening
that interfere with either the ability to attain/demonstrate functional measures or
interferes with ability to receive intrathecal (IT) dosing
• Severe scoliosis (defined as ≥ 50° curvature of spine) evident on X-ray examination
• Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose
administration
• Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse
oximetry < 95% saturation at screening while the patient is awake, or for high
altitudes > 1000 m, oxygen saturation < 92% while the patient is awake
• Pulse oximetry saturation must not decrease ≥ four (4) percentage points between
screening and highest value on day of dosing
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over
the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given
by non-oral methods (i.e., nasogastric tube or nasojejunal tube) or patients whose
weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards
(Onis 2006). Placement of a permanent gastrostomy prior to screening is not an
exclusion
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over
the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given
by non-oral methods or patients whose weight-for-age falls below the 3rd percentile
based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy
prior to screening is not an exclusion
• Active viral infection (includes human immunodeficiency virus (HIV) or serology
positive for hepatitis B or C, or Zika virus)
• Serious non-respiratory tract illness requiring systemic treatment and/or
hospitalization within two (2) weeks prior to study entry
• Respiratory infection requiring medical attention, medical intervention or increase in
supportive care of any manner within four (4) weeks prior to study entry
• Severe non-pulmonary/respiratory tract infection within four (4) weeks before study
dosing or concomitant illness that in the opinion of the Principal Investigator (PI)
creates unnecessary risks for gene transfer such as:
• Major renal or hepatic impairment
• Known seizure disorder
• Diabetes mellitus
• Idiopathic hypocalciuria
• Symptomatic cardiomyopathy
• History of bacterial meningitis or brain or spinal cord disease, including tumors, or
abnormalities by magnetic resonance imaging (MRI) or computerized tomography (CT) that
would interfere with the lumbar puncture (LP) procedures or CSF circulation
• Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or
their excipients
• Known allergy or hypersensitivity to iodine or iodine-containing products
• Concomitant use of any of the following: drugs for treatment of myopathy or
neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive
therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive
therapy within 3 months of study dosing
• Inability to withhold use of laxatives or diuretics in the 24 hours prior to dose
administration
• Anti-AAV9 antibody titers >1:50 as determined by Enzyme-linked Immunosorbent Assay
(ELISA) binding immunoassay
• Should a potential patient demonstrate anti AAV9 antibody titer > 1:50, he or she
may receive retesting within 30 days of the screening period and will be eligible
to participate if the anti AAV9 antibody titer upon retesting is ≤ 1:50
• Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total
bilirubin > 2 × ULN, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] < 8 or > 18 g/dL; white
blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy. Patients with an
elevated bilirubin level that is unequivocally the result of neonatal jaundice shall
not be excluded
• Participation in recent SMA treatment clinical trial or receipt of an investigational
or approved compound product or therapy received with the intent to treat SMA at any
time prior to screening for this study
• Oral beta agonists must be discontinued 30 days prior to dosing.
• Inhaled albuterol specifically prescribed for the purposes of respiratory
(bronchodilator) management is acceptable and not a contraindication at any time
prior to screening for this study
• Expectation of major surgical procedures during the 1-year study assessment period
A Study of Galcanezumab (LY2951742) in Participants 6 to 17 Years of Age With Episodic Migraine (REBUILD-1)
The main purpose of this study is to evaulate the efficacy and safety of galcanezumab in
participants 6 to 17 years of age for the preventive treatment of episodic migraine. The
primary objective is to demonstrate the superiority of galcanezumab versus placebo in the
reduction of monthly migraine headache days across the 3-month double-blind treatment period.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Eric Remster
150068
All
6 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03432286
STU 072018-085
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Inclusion Criteria:
• Have a diagnosis of migraine with or without aura as defined by the IHS ICHD-3
guidelines (1.1 or 1.2 according to ICHD-3 [2018]), with a history of migraine
headaches of at least 6 months prior to screening.
Exclusion Criteria:
• Participants who are taking, or are expected to take, therapeutic antibodies during
the course of the study (adalimumab, infliximab, trastuzumab, bevacizumab, etc.).
Prior use of therapeutic antibodies, other than antibodies to calcitonin gene-related
peptide (CGRP) or its receptor, is allowed if that use was more than 12 months prior
to baseline.
• Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic
proteins, or to galcanezumab or its excipients.
• Current use or prior exposure to galcanezumab, another CGRP antibody, or CGRP receptor
antibody, including those who have previously completed or withdrawn from this study
or any other study investigating a CGRP antibody.
• History of persistent daily headache, cluster headache or migraine subtypes including
hemiplegic (sporadic or familial) migraine and migraine with brainstem aura
(previously basilar-type migraine) as defined by IHS ICHD-3.
• History of significant head or neck injury within 6 months prior to screening; or
traumatic head injury at any time that is associated with significant change in the
quality or frequency of their headaches, including new onset of migraine following
traumatic head injury.
• Participants with a known history of intracranial tumors or developmental
malformations including Chiari malformations.
A Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy
This study will evaluate the long-term safety and tolerability of VX-445 in triple
combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis
(CF) who are homozygous or heterozygous for the F508del mutation
Call 214-648-5005 studyfinder@utsouthwestern.edu
Raksha Jain
19733
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03525574
STU 022018-086
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Inclusion Criteria:
• Completed study drug treatment in a parent study; or had study drug interruption(s) in
a parent study but completed study visits up to the last scheduled visit of the
Treatment Period in the parent study.
Exclusion Criteria:
• History of drug intolerance in a parent study that would pose an additional risk to
the subject in the opinion of the investigator.
• Current participation in an investigational drug trial (other than a parent study)
Other protocol defined Inclusion/Exclusion criteria may apply.
Drug: VX-445, Drug: TEZ, Drug: IVA, Drug: IVA
Cystic Fibrosis, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects 1 to Less Than 2 Years of Age With Cystic Fibrosis, Homozygous for F508del
This study will evaluate the safety and pharmacokinetics (PK) of lumacaftor (LUM) and
ivacaftor (IVA) in subjects 1 to less than 2 years of age with cystic fibrosis (CF),
homozygous for F508del (F/F).
Call 214-648-5005 studyfinder@utsouthwestern.edu
Preeti Sharma
117060
All
12 Months to 23 Months old
Phase 3
This study is NOT accepting healthy volunteers
NCT03601637
STU 052018-060
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Key
Inclusion Criteria:
• Subjects will be 1 to less than 2 years of age on Day 1 of the relevant part of the
study.
• Homozygous for F508del (F/F).
Key
Exclusion Criteria:
• Any clinically significant laboratory abnormalities at the Screening Visit that would
interfere with the study assessments or pose an undue risk for the subject.
• Solid organ or hematological transplantation.
Other protocol defined Inclusion/Exclusion criteria may apply.
Establishing Efficacy of an Inpatient Intervention and Phone App to Reduce Suicidal Risk (ASAP+BRITE)
In this 2-site study, University of Texas Southwestern Medical Center (UTSW) and Western
Psychiatric Institute and Clinic (WPIC), the investigators will conduct a randomized clinical
trial (RCT) in 240 psychiatrically hospitalized suicidal adolescents, examining the single
and additive effects of two components of an inpatient unit intervention for suicidal
adolescents, As Safe As Possible (ASAP), which focuses on emotion regulation and safety
planning, and an emotion regulation/safety plan phone app (BRITE).
Call 214-648-5005 studyfinder@utsouthwestern.edu
Beth Kennard
13826
All
12 Years to 17 Years old
N/A
This study is NOT accepting healthy volunteers
NCT03825588
STU 112016-057
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Inclusion Criteria:
• Youth admitted to the inpatient unit at either site for a recent suicide attempt or
significant suicidal ideation with a plan or intent.
• The youth and parent are able to complete assessments in English, and the youth is
able to complete therapy.
Exclusion Criteria:
• The youth currently exhibits psychosis.
• The youth currently exhibits mania.
• The youth is currently <85% of their ideal body weight.
• The youth is intellectually incapable of completing the study, e.g. has an
intelligence quotient (IQ) < 70.
Behavioral: ASAP (As Safe As Possible), Behavioral: BRITE smart phone app, Behavioral: TAU (treatment as usual)
A Study of LOXO-292 in Participants 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 participants with advanced solid tumors,
including rearranged during transfection (RET)-fusion-positive solid tumors, medullary
thyroid cancer (MTC) and other tumors with RET activation.
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which 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 multikinase inhibitors (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) greater than or equal to (≥) 40 percent (%) (age less than [<] 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: Participants 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 participants with evidence of a RET gene
alteration in tumor
• 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:
• Without measurable disease but otherwise meet criteria for Cohorts 1 and 2;
• 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: Participants 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
• Cohort 7: Participants must have a histologically confirmed stage IB-IIIA NSCLC by
AJCC (The American Joint Committee on Cancer) version 8. The tumor must have been
deemed resectable by a thoracic surgeon, the participant must be determined to be
medically operable based on the determination of a thoracic surgeon, and the
participant must not have received prior systemic therapy, including prior radiation
therapy, for NSCLC.
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: Participants
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 participants 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 Common Terminology Criteria
for Adverse Events (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. Participants 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) greater than (>) 470 milliseconds
(msec)
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers and certain prohibited concomitant medications
• Stratum I
• Patients must be less than 18 years of age at the time of diagnosis.
• Patients must have histological verification of the diagnosis of Langerhans cell
histiocytosis according to the criteria described in Section 6.1
• Signed informed consent form
• Stratum II
• Patients of Stratum I who have:
• Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
• AD intermediate or worse in non-risk organs or AD better in risk organs after 12
weeks (Initial Course 2)
• Disease progression (AD worse) in non-risk organs at any time during continuation
treatment
• Active disease at the end of Stratum I treatment
• Disease reactivation in non-risk organs at any time after completion of Stratum I
treatment
• Stratum III
• Patients from Stratum I who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD
intermediate in risk organs after week 12 (after Initial Course 2).
• Presence of unequivocally severe organ dysfunction at the above mentioned
evaluation points (hematological dysfunction, liver dysfunction, or both of them)
as
• Hb <70 g/L (<7.0 g/dl) and/or transfusion dependency
• PLT <20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have
to be fulfilled) AND/OR
• Liver dysfunction (or digestive involvement with protein loss)
• Total protein <55 g/L or substitution dependency
• Albumin <25 g/L or substitution dependency (at least one of the two criteria
to be fulfilled)
• Stratum IV
• Patients from Stratum I or Stratum III who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD
intermediate in risk organs after week 12 (after Initial Course 2) of Stratum I
OR
• AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD
intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
• Presence of unequivocally severe organ dysfunction at the above mentioned
evaluation points (hematological dysfunction, liver dysfunction, or both of them)
as defined in Table XI (see Section 10.3.1).
• Informed consent: All patients or their legal guardians (if the patient is <18
years of age) must sign an Ethics or institutional Review Board approved consent
form indicating their awareness of the investigational nature and the risks of
this study. When appropriate, younger patients will be included in all
discussions in order to obtain assent.
• Adequate organ function: Patients should have adequate hepatic, renal, cardiac
and pulmonary function to undergo reduced intensity HCT based upon local
institutional guidelines, or at a minimum meet requirements noted in eligibility
checklist Appendix A-VIII_1. However, significant hepatic and pulmonary
dysfunction, if secondary to underlying LCH disease activity, will not exclude
patients from protocol enrollment and should be discussed with the National PI
Coordinator and the Coordinating Principal Investigator.
• Stratum V
• All patients with verified diagnosis of LCH and MRI findings consistent with
ND-CNSLCH irrespective of previous treatments (also those not registered to other
Strata ofLCH-IV).
• Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion
in the hypothalamus-pituitary axis). In patients with already established
diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a
biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion
is needed for inclusion into the study
• Stratum VI
-- Patients with newly diagnosed SS-LCH and localization other than "multifocal
bone",isolated tumorous CNS lesion, or isolated "CNS-risk" lesion.
• Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as
consent for longterm follow-up has not been withheld.
Exclusion Criteria:
• Stratum I
• Pregnancy (patients of child-bearing age must be appropriately tested before
chemotherapy)
• LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis,
lung fibrosis, etc.) in the absence of active disease
• Prior systemic therapy
• Stratum II
• Patients with progressive disease in risk organs
• Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without
evidence of active LCH in the same organ or in any other locations
• No written consent of the patient or his/her parents or legal guardian
• Stratum III
• The presence of any of the following criteria will exclude the patient from the
study:
• Isolated sclerosing cholangitis without evidence of active hepatic LCH as the
only evidence of risk organ involvement.
• Inadequate renal function as defined by serum creatinine > 3x normal for age
• Stratum IV
• Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
• Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
• Uncontrolled active life-threatening infection.
• Decreased renal function with a GFR of less than 50ml/1.73m2/min.
• Pregnancy or active breast feeding
• Failure to provide signed informed consent
• Stratum VI
• Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible
for Stratum V),
• Patients with isolated "CNS-risk" or multifocal bone lesions (they are eligible
for Stratum I, Group 2)
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.
A Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients
MPS IIIA, also known as Sanfilippo A, is an inherited lysosomal storage disease (LSD). MPS
IIIA is caused by a deficiency in sulfamidase, one of the enzymes involved in the lysosomal
degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The natural course of MPS
IIIA is characterized by devastating neurodegeneration with initially mild somatic
involvement. The aim of the present study is to assess the safety, tolerability and efficacy
of long-term SOBI003 treatment. SOBI003 is a chemically modified recombinant human (rh)
Sulfamidase developed as an enzyme replacement therapy (ERT).
Call 214-648-5005 studyfinder@utsouthwestern.edu
Luis Umana Franco
150802
All
18 Months to 78 Months old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03811028
STU-2019-0796
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Inclusion Criteria:
• Completion of study SOBI003-001
• Informed consent obtained from the patient´s legally authorized representative
Exclusion Criteria:
• If, in the opinion of the investigator, there are patient specific safety concerns
that contraindicates further treatment with SOBI003
Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma
This phase II trial studies how well the combination of dabrafenib and trametinib works after
radiation therapy in children and young adults with high grade glioma who have a genetic
change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells
and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells
by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their
growth. Giving dabrafenib with trametinib after radiation therapy may work better than
treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade
glioma.
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient is suspected of having
localized newly-diagnosed HGG, excluding metastatic disease
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient and/or their parents or legal
guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Specimens obtained at the time of
diagnostic biopsy must be submitted through APEC14B1 as soon as possible (ASAP),
preferably within 13 calendar days of the procedure.
• Patients must be >= 3 years and =< 21 years of age at the time of enrollment
• Patients must have eligibility confirmed by Rapid Central Pathology and Molecular
Screening Reviews performed on APEC14B1
• Newly diagnosed high-grade glioma with BRAFV600-mutation
• Positive or negative results for H3 K27M by immunohistochemistry (IHC)
• Histologically confirmed high-grade glioma (World Health Organization [WHO] grade
III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic
pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG),
glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS)
• Patients must have had histologic verification of a high-grade glioma diagnosis.
Cerebrospinal fluid (CSF) cytology by lumbar puncture must be done if clinically
indicated and determined to be safe prior to study enrollment. If cytology proves
positive, the patient would be considered to have metastatic disease and would,
therefore, be ineligible.
• A pre- and post-operative brain magnetic resonance imaging (MRI) with and without
contrast and a baseline spine MRI with contrast must be obtained prior to enrollment.
The requirement for a post-operative MRI is waived for patients who undergo biopsy
only. If the spine MRI is positive, the patient would be considered to have metastatic
disease and would be ineligible.
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age.
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment).
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age 3 to < 6 years (Male 0.8 mg/dL, Female 0.8 mg/dL)
• Age 6 to < 10 years (Male 1 mg/dL, Female 1 mg/dL)
• Age 10 to < 13 years (Male 1.2 mg/dL, Female 1.2 mg/dL)
• Age 13 to 16 < years (Male 1.5 mg/dL, Female 1.4 mg/dL)
• Age >= 16 years (Male 1.7 mg/dL, Female 1.4 mg/dL)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment), and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for
SGPT is 45 U/L.
• Patients with a seizure disorder may be enrolled if their seizures are well controlled
while on non-enzyme inducing anticonvulsants permitted on this study.
• Patients must be enrolled and protocol therapy must be projected to begin no later
than 31 days after definitive surgery (day 0). If a biopsy only was performed, the
biopsy date will be considered the date of definitive surgery. For patients who have a
biopsy or incomplete resection at diagnosis followed by additional surgery, the date
of the last resection will be considered the date of definitive surgery.
• 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 intrinsic brainstem or primary spinal cord tumors will be excluded.
• Patients with metastatic disease (defined as neuraxis dissemination either by imaging
or by cytology) will be excluded.
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant for the
treatment of HGG other than surgical intervention and/or corticosteroids.
• Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK
inhibitor, or an ERK inhibitor.
• Patients with a history of a malignancy with confirmed activating RAS mutation.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dabrafenib, trametinib, and their excipients.
• Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease,
or uncontrolled infection), psychological, familial, sociological, or geographical
conditions that do not permit compliance with the protocol; or unwillingness or
inability to follow the procedures required in the protocol.
• Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel
or large bowel resection) that will interfere significantly with the absorption of
drugs.
• History of hepatitis B virus, or hepatitis C virus infection (patients with laboratory
evidence of cleared hepatitis B virus and/or hepatitis C virus may be enrolled).
• History or current diagnosis of cardiac disease indicating significant risk of safety
for patients participating in the study such as uncontrolled or significant cardiac
disease, including any of the following:
• Recent myocardial infarction (within the last 6 months);
• Uncontrolled congestive heart failure;
• Unstable angina (within last 6 months);
• Clinically significant (symptomatic) or known, uncontrolled cardiac arrhythmias
(e.g., sustained ventricular tachycardia, and clinically significant second or
third degree atrioventricular [AV] block without a pacemaker) except sinus
arrhythmia within the past 24 weeks prior to the first dose of study treatment;
• Coronary angioplasty or stenting (within last 6 months);
• Intra-cardiac defibrillators;
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram.
• Patients with a history or current evidence of retinal vein occlusion (RVO) or central
serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g., uncontrolled
glaucoma or ocular hypertension).
• Patients with presence of interstitial lung disease or pneumonitis.
• Female patients who are pregnant are ineligible since there is yet no available
information regarding human fetal or teratogenic toxicities.
• Lactating females are not eligible unless they have agreed not to breastfeed their
infants for the duration of the study and for 4 months following discontinuation of
study therapy.
• Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained.
• Sexually active patients of reproductive potential (male or female) are not eligible
unless they have agreed to use an effective contraceptive method for the duration of
their study participation and for 4 months following discontinuation of study therapy.
Male patients (including those who have had a vasectomy) taking dabrafenib and
trametinib combination therapy must use a condom during intercourse while on study and
for 16 weeks after stopping treatment, and should not father a child during these
periods. Women of childbearing potential should use effective non-hormonal
contraception during therapy and for 4 weeks following discontinuation of dabrafenib
and at least 4 months following the last dose of trametinib in patients taking
combination therapy. Women should be advised that dabrafenib may decrease the efficacy
of hormonal contraceptives and an alternate method of contraception, such as barrier
methods, should be used.
Glioblastoma, Malignant Glioma, Anaplastic Astrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, Anaplastic Ganglioglioma, WHO Grade III Glioma, Brain and Nervous System
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the
maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose
(RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an
ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction.
Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded
Independent Central Review (BICR) of repotrectinib in each subject population expansion
cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene
rearrangement. The secondary objective will include the duration of response (DOR), time to
response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit
rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a
ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic
solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on
Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by
protocol specified tests.
2. ECOG PS 0-1.
3. Age ≥18 (or age ≥ 20 of age as required by local regulation).
4. Capability to swallow capsules intact (without chewing, crushing, or opening).
5. At least 1 measurable target lesion according to RECIST version 1.1. CNS-only
measurable disease as defined by RECIST version 1.1 is allowed.
6. Prior cytotoxic chemotherapy is allowed.
7. Prior immunotherapy is allowed.
8. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer
therapy to National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI CTCAE) Version 4.03 Grade less than or equal to 1.
9. Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic
leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol
specified criteria.
10. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils
count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L);
Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine
clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN;
Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present
Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are
present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or
without supplementation
11. Life expectancy ≥ 3 months.
PHASE 2 Key Inclusion Criteria
1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic
solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene
fusion.
2. Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based
local testing using either:
1. a next-generation sequencing (NGS) or quantitative polymerase chain reaction
(qPCR) test will be accepted to determine molecular eligibility.
• Adequate tumor tissue needs to be sent to the Sponsor designated central
diagnostic laboratory for retrospective confirmation by a central diagnostic
laboratory test selected by the Sponsor.
OR
2. a fluorescence in situ hybridization (FISH) test AND prospective confirmation of
fusion status by a central diagnostic laboratory test selected by the Sponsor
PRIOR to enrollment will be accepted to determine molecular eligibility.
• Adequate tumor tissue must be sent to the Sponsor designated central
diagnostic laboratory for prospective confirmation by a central diagnostic
laboratory test selected by the Sponsor PRIOR to enrollment.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
4. Age ≥12 (or age ≥ 20 as required by local regulation).
5. Willing and able to provide written institutional review board (IRB)/institutional
ethics committee-approved Informed Consent or an Assent signed by a parent or legal
guardian for subjects age 12 to 17.
6. At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed
by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to
enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST
(v1.1) are eligible.
7. Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3
rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all
inclusion and exclusion criteria are met.
i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based
chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv.
EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+
solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
8. Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic
leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol
specified criteria.
9. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils
count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L);
Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine
clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases
(ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline
phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present;
Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without
supplementation
10. Life expectancy ≥ 3 months.
Key Exclusion Criteria PHASE 1 and PHASE 2
1. Concurrent participation in another therapeutic clinical trial.
2. Symptomatic brain metastases or leptomeningeal involvement.
3. History of previous cancer, except for squamous cell or basal-cell carcinoma of the
skin, or any in situ carcinoma that has been completely resected, requiring therapy
within the previous 2 years.
4. Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy
(except palliative to relieve bone pain) within 2 weeks of study entry. Palliative
radiation (≤10 fractions) must have been completed at least 48 hours prior to study
entry
5. Clinically significant cardiovascular disease (either active or within 6 months prior
to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery
bypass graft, symptomatic congestive heart failure (New York Heart Association
Classification Class ≥ II), cerebrovascular accident or transient ischemic attack,
symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac
dysrhythmias of NCI CTCAE grade ≥2
6. Any of the following cardiac criteria:
Mean resting corrected QT interval (ECG interval measured from the onset of the QRS
complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3
ECGs, using the screening clinic ECG machine-derived QTc value Any clinically
important abnormalities in rhythm, conduction or morphology of resting ECG (e.g.,
complete left bundle branch block, third degree heart block, second degree heart
block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation
or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT
syndrome, family history of long QT syndrome, or any concomitant medication known to
prolong the QT interval.
7. Known active infections (bacterial, fungal, viral including HIV positivity).
8. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut
syndrome) or other malabsorption syndromes that would impact drug absorption.
9. Peripheral neuropathy of CTCAE ≥grade 2.
10. History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4
interstitial fibrosis or interstitial lung disease including a history of pneumonitis,
hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease,
obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior
radiation pneumonitis are not excluded.
Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy
This study will evaluate the long-term safety, efficacy, and pharmacodynamics of elexacaftor
(ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in
subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a gating
or residual function mutation (F/G and F/RF genotypes).
Call 214-648-5005 studyfinder@utsouthwestern.edu
Raksha Jain
19733
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04058366
STU-2019-1109
Show full eligibility criteria
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Key
Inclusion Criteria:
• Completed study drug treatment in parent study (VX18-445-104); or had study drug
interruption(s) in parent study but completed study visits up to the last scheduled
visit of the Treatment Period in the parent study
Key
Exclusion Criteria:
• History of study drug intolerance in parent study
Other protocol defined Inclusion/Exclusion criteria may apply
Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled
study comparing the efficacy of vorasidenib to placebo in participants with residual or
recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their
only treatment. Participants will be required to have central confirmation of IDH mutation
status prior to randomization. Approximately 340 participants are planned to be randomized
1:1 to receive orally administered vorasidenib 40 mg QD or placebo.
• Be at least 12 years of age and weigh at least 40 kg.
• Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.
• Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total
resection), with the most recent surgery having occurred at least 1 year (-1 month)
and not more than 5 years (+3 months) before the date of randomization, and no other
prior anticancer therapy, including chemotherapy and radiotherapy and not be in need
of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
• Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2
R172K/M/W/S/G mutation variants tested) gene mutation status disease by central
laboratory testing during the Prescreening period and available 1p19q status by local
testing (eg, fluorescence in situ hybridization [FISH], comparative genomic
hybridization [CGH] array, sequencing) using an accredited laboratory.
• Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC.
• Have a Karnofsky Performance Scale (KPS) score (for participants ≥16 years of age) or
Lansky Play Performance Scale (LPPS) score (for participants <16 years of age) of
≥80%.
Key
Exclusion Criteria:
• Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection,
gross-total resection) for treatment of glioma including systemic chemotherapy,
radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser
ablation, etc.
• Have features assessed as high-risk by the Investigator, including brainstem
involvement either as primary location or by tumor extension, clinically relevant
functional or neurocognitive deficits due to the tumor in the opinion of the
Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures
(defined as persistent seizures interfering with activities of daily life AND failed 3
lines of antiepileptic drug regimens including at least 1 combination regimen).
Drug: Vorasidenib, Drug: Matching Placebo
Recurrent Glioma, Grade 2 Glioma, Residual Glioma, Brain and Nervous System
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
Follow-up of the EPITOPE Study to Evaluate Long-term Efficacy and Safety of DBV712 in Young Children (EPOPEX)
Open-label, follow-up study for subjects who completed the EPITOPE study.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Christopher Parrish
168280
All
2 Years to 4 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03859700
STU-2019-1180
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Inclusion Criteria:
• completion of the EPITOPE study
Exclusion Criteria:
• Generalized dermatologic disease (for example, active atopic dermatitis, uncontrolled
generalized active eczema, ichthyosis vulgaris) extending widely on the skin and
especially on the back or arms with no intact zones to apply the Viaskin patches.
• Diagnosis of asthma that evolved to severe, unstable or uncontrolled asthma
Compatibility of C7 With Ketogenic Diet in Patients Diagnosed With G1D
To explore triheptanoin (C7 oil) compatibility with the ketogenic diet by evaluating EEG, and
seizure rate, glycemia and ketosis in proven G1D patients receiving a ketogenic diet.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Juan Pascual
85158
All
30 Months to 35 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03301532
STU 102015-091
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Inclusion Criteria:
• Diagnosis of glucose transporter type 1 deficiency (G1D), confirmed by clinical
genotyping at a CLIA-certified laboratory.
• Stable on ketogenic diet at 2.5:1 to 4:1 ratio (i.e., no changes in ratio will have
taken place for 2 months). The initiation of a ketogenic diet is previous to •and
thus is not part of this study.
• Males and females 30 months to 35 years and 11 months old inclusive.
Exclusion Criteria:
• Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
• Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome,
crohn's disease, or colitis that could increase the subject's risk of developing
diarrhea or stomach pain.
• Subjects with a BMI (body mass index) greater than or equal to 30.
• Subjects currently not on ketogenic diet.
• Women who are pregnant or breast feeding may not participate. Women who plan to become
pregnant during the course of the study, or who are unwilling to use birth control to
prevent pregnancy (including abstinence) may not participate. Females age 10 and over
will be asked to provide a urine sample for a pregnancy test via dipstick. Subjects
will be asked to agree to abstinence or another form of birth control for the duration
of the study.
• Allergy/sensitivity to C7
• Previous use of triheptanoin less than 1 month prior to study initiation.
• Treatment with medium chain triglycerides in the last 24 hours.
• Subjects exhibiting signs of dementia, or diagnosed with any degenerative brain
disorder (such as Alzheimer's disease) that would confound assessment of cognitive
changes, in the opinion of the investigator.
• Active drug or alcohol use or dependence that, in the opinion of the investigator,
would interfere with adherence to study requirements.
• Inability or unwillingness of subject or legal guardian/representative to give written
informed consent, or assent for children age 10-17,
• Addition of a new antiseizure drug in the previous 3 months.
A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
This phase II trial studies the side effects and how well nirogacestat works in treating
patients with desmoid tumors that has grown after at least one form of treatment by mouth or
in the vein that cannot be removed by surgery. Nirogacestat may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth.
• Patients must have a body surface area of > 0.3 m^2 at the time of enrollment
• Existing or recurrent desmoid tumor that is deemed not amenable to surgery without
significant morbidity and progressed by >= 10% as assessed by RECIST version (v)1.1
within the 6-month period prior to study enrollment
• Patients must have had histologic verification of the desmoid tumor
• Patients must have measurable disease by RECIST v1.1 criteria
• Patient must have received at least one prior course of systemic therapy for
desmoid tumor
• Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for
patients > 16 years of age) performance status score of >= 50. Patients who are unable
to walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing performance score
• Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, surgery or radiotherapy prior to entering this study.
Patients may not be using or anticipate using these treatments after the observed
progression or within the time period stated below
• Cytotoxic chemotherapy: must not have received within 2 weeks of entry onto this
study (4 weeks if prior nitrosourea)
• Small molecule tyrosine kinase inhibitors (e.g., sorafenib, pazopanib, imatinib),
rapalogs (e.g., temsirolimus, everolimus, sirolimus) or anti estrogen therapy
(e.g., tamoxifen): may not have received within 28 days prior to the first dose
of study treatment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy
with a biologic agent
• Local regional tumor directed therapy, including, but not limited to small port
radiation therapy (RT), radiofrequency ablation, cryotherapy, surgery: at least 2
weeks since these therapies and all toxicity must have resolved to grade =< 1. If
prior craniospinal RT or if >= 50% radiation of pelvis then >= 6 months must have
elapsed. If other substantial bone marrow (BM) radiation, then >= 6 weeks must
have elapsed
• Stem cell transplant (SCT): No evidence of active graft versus (vs.) host
disease. For allogeneic SCT, >= 6 months must have elapsed
• No prior gamma-secretase, Notch or beta-catenin inhibitor
• Investigational drugs: must not have received investigational drug within 4 weeks
of study entry, and all toxicities related to prior therapy must be resolved to
grade =< 1 or baseline
• Concomitant Medication Restrictions
• Steroids: patients who are receiving dexamethasone must be on a stable or
tapering dose for at least 2 weeks prior to study entry. Use of steroids for
non-tumor indications (e.g., asthma or severe allergic reaction) is permitted
• Growth factor(s): must not have received within 1 week of entry onto this study
• Patients who are currently receiving drugs that are strong inducers or moderate
to strong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate to
strong inhibitors of CYP3A4 are not allowed from 14 days prior to enrollment to
the end of protocol therapy. Note: CYP3A4 inducing anti-epileptic drugs on a
stable dose, are allowed
• Must not be receiving non-steroidal anti-inflammatory drugs (NSAIDs) as treatment
for desmoid tumor after the observed progression and patient agrees to not use
NSAIDs while on study. Occasional use (defined as =< 3 times per week) for
treatment of pain is permitted
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment)
• Hemoglobin >= 9.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to enrollment)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days
prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male and female)
• Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male and female)
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male and female)
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male and female)
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (unless secondary to
previously diagnosed Gilbert's syndrome) (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L (within 7 days prior to enrollment)
• Adequate cardiac function defined as:
• Corrected QT (QTc) interval < 470 ms
• No history of congenital or acquired prolonged QTc syndrome
• No history of clinically significant cardiac arrhythmias, congestive heart
failure, stroke or myocardial infarction within 6 months prior to study entry
• 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:
• Active or chronic infection within 7 days prior to study entry
• Patients with gastrointestinal conditions that might predispose for drug
intolerability or poor drug absorption (e.g., inability to take oral medication, prior
surgical procedures affecting absorption (e.g., gastric bypass), malabsorption
syndrome, and active peptic ulcer disease)
• Patients with ulcerative colitis, inflammatory bowel disease, or a partial or complete
small bowel obstruction
• Known active infection with hepatitis B, hepatitis C or human immunodeficiency virus
(HIV)
• Patients with a prior history of malignancy, with the exceptions of desmoid tumor(s)
and non-melanoma skin cancer, who are not in remission for more than 3 years
• Patients who are unable to swallow tablets. Tablets must not be crushed or chewed.
Administration of nirogacestat via gastrostomy tube or nasogastric tube is not allowed
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study
• Sexually active female patients of reproductive potential who have not agreed to use 1
method of highly effective contraceptive (including copper-containing intrauterine
device, condom with spermicidal foam/gel/film/cream/suppository, bilateral tubal
ligation, established use of inserted, injected or implanted hormonal method of
contraception, abstinence, or male sterilization) for the duration of their study
participation and for at least 6 months after last dose of nirogacestat. A second form
of contraception (i.e. barrier method) is required for patients who are using hormonal
contraception as nirogacestat may reduce the efficacy of hormonal contraceptives
• Sexually active male patients of reproductive potential who have not agreed to use a
condom and their female partner who have not agreed to use one of the highly effective
methods of contraception mentioned above during treatment and for at least 90 days
after the last dose of nirogacestat
• Female patients who are breastfeeding
• Female patients who are pregnant. These patients are excluded because there is no
available information regarding the effects of nirogacestat on the developing human
fetus and inhibition of gamma-secretase is known to be teratogenic
• Female patients of childbearing potential unless a negative pregnancy test result has
been obtained
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.
Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
This phase III trial studies how well response and biology-based risk factor-guided therapy
works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may
not need treatment until it progresses. In this case, observation may be sufficient.
Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and
what the best treatment is. Response and biology-based risk factor-guided therapy may be
effective in treating patients with non-high risk neuroblastoma and may help to avoid some of
the risks and side effects related to standard treatment.
• Patients must be:
• < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
• < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms
neuroblastoma/ganglioneuroblastoma
• Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
• Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene
neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International
Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN
non-amplified ganglioneuroblastoma verified by histology
• Patients must meet the specified criteria for one of the treatment groups defined
below; genomic features include MYCN gene amplification, segmental chromosome
aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number
gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
• "Favorable" genomic features are defined by one or more whole-chromosome gains or
hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome
aberrations as defined above
• "Unfavorable" genomic features are defined by the presence of any segmental
chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic
copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this
includes copy neutral loss of heterozygosity (LOH)
• Only patients with MYCN non-amplified tumors are eligible for this study
• Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1
neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
• Patients with non-adrenal primaries are eligible, but must have positive uptake
on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites
(urine or serum) to support the diagnosis of neuroblastoma
• No prior tumor resection or biopsy
• Group A will be further split into two subsets, which are mutually exclusive, for
statistical purposes
• Group A1:
• > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in
greatest diameter OR
• Patients less than 6 months of age with an adrenal primary tumor > 3.1 and <
5 cm in greatest diameter OR
• < 12 months of age with a non-adrenal primary site < 5 cm in greatest
diameter
• Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in
greatest diameter.
• Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2
neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• No life threatening symptoms or no impending neurologic or other organ function
compromise (e.g. epidural or intraspinal tumors with existing or impending
neurologic impairment, periorbital or calvarial-based lesions with existing or
impending cranial nerve impairment, anatomic or mechanical compromise of critical
organ function by tumor [abdominal compartment syndrome, urinary obstruction,
etc.]); horner syndrome is not considered neurologic compromise
• No prior tumor resection, tumor biopsy ONLY
• Only patients with both favorable histology and favorable genomic features will
remain on study as part of Group B; the institution will be notified of
histologic and genomic results within 3 weeks of specimen submission on ANBL00B1
or APEC14B1
• Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms
neuroblastoma/ganglioneuroblastoma
• No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is
allowed
• 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 MYCN amplified tumors are not eligible
• Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive
diagnostic procedure
• Group A and C patients, not required to undergo tumor biopsy, who do not enroll on
ANBL1232 within 4 weeks of confirmatory imaging study
The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study
This research study is evaluating the use of specialized testing of solid tumors including
sequencing. The process of performing these specialized tests is called tumor profiling. The
tumor profiling may result in identifying changes in genes of the tumor that indicate that a
particular therapy may have activity. This is called an individualized cancer therapy (iCat)
recommendation. The results of the tumor profiling and, if applicable, the iCat
recommendation will be returned.
• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or
complete remission
• Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence
--- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .
Exclusion Criteria:
• No Therapy Planned
-- Patients who have declined further anticancer therapy will be excluded.
• Performance Status
-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.
Genetic: Genetic testing and GAIN report
Sarcoma, Pediatric Solid Tumor, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, 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, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Heart, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
Historically, medulloblastoma treatment has been determined by the amount of leftover disease
present after surgery, also known as clinical risk (standard vs. high risk). Recent studies
have shown that medulloblastoma is made up of distinct molecular subgroups which respond
differently to treatment. This suggests that clinical risk alone is not adequate to identify
actual risk of recurrence. In order to address this, we will stratify medulloblastoma
treatment in this phase II clinical trial based on both clinical risk (low, standard,
intermediate, or high risk) and molecular subtype (WNT, SHH, or Non-WNT Non-SHH). This
stratified clinical and molecular treatment approach will be used to evaluate the following:
- To find out if participants with low-risk WNT tumors can be treated with a lower dose of
radiation to the brain and spine, and a lower dose of the chemotherapy drug
cyclophosphamide while still achieving the same survival rate as past St. Jude studies
with fewer side effects.
- To find out if adding targeted chemotherapy after standard chemotherapy will benefit
participants with SHH positive tumors.
- To find out if adding new chemotherapy agents to the standard chemotherapy will improve
the outcome for intermediate and high risk Non-WNT Non-SHH tumors.
- To define the cure rate for standard risk Non-WNT Non-SHH tumors treated with reduced
dose cyclophosphamide and compare this to participants from the past St. Jude study.
All participants on this study will have surgery to remove as much of the primary tumor as
safely possible, radiation therapy, and chemotherapy. The amount of radiation therapy and
type of chemotherapy received will be determined by the participant's treatment stratum.
Treatment stratum assignment will be based on the tumor's molecular subgroup assignment and
clinical risk.
The participant will be assigned to one of three medulloblastoma subgroups determined by
analysis of the tumor tissue for tumor biomarkers:
- WNT (Strata W): positive for WNT biomarkers
- SHH (Strata S): positive for SHH biomarkers
- Non-WNT Non-SHH, Failed, or Indeterminate (Strata N): negative for WNT and SHH
biomarkers or results are indeterminable
Participants will then be assigned to a clinical risk group (low, standard, intermediate, or
high) based on assessment of:
- How much tumor is left after surgery
- If the cancer has spread to other sites outside the brain [i.e., to the spinal cord or
within the fluid surrounding the spinal cord, called cerebrospinal fluid (CSF)]
- The appearance of the tumor cells under the microscope
- Whether or not there are chromosomal abnormalities in the tumor, and if present, what
type (also called cytogenetics analysis)
INCLUSION CRITERIA
• Medulloblastoma or medulloblastoma variants including posterior fossa PNET as
documented by an institutional pathologist.
• Participant's age meets one of the following: (1) Age greater than or equal to 3 years
and less than 22 years of age at the time of diagnosis (may enroll on Strata W, S or
N), OR (2) age is greater than or equal to 22 years and less than 40 years AND patient
has SHH medulloblastoma (must enroll on Stratum S).
• No previous radiotherapy, chemotherapy or other brain tumor directed therapy other
than corticosteroid therapy and surgery.
• Patients must begin treatment as outlined in the protocol within 36 days of definitive
surgery (day of surgery is day 0; definitive surgery includes second surgeries to
resect residual tumor).
• Adequate performance status: children < 10-Lansky Score ≥ 30; children ≥ 10-Karnofsky
≥ 30 (except for posterior fossa syndrome).
• Females of child-bearing potential cannot be pregnant or breast-feeding. Female
participants > 10 years of age or post-menarche must have a negative serum or urine
pregnancy test prior to enrollment.
• Biological parent(s) of participant (child) enrolling on this protocol. These parents
will be assigned to cohort P. The exclusion criteria below do not apply to this
cohort.
EXCLUSION CRITERIA
• CNS embryonal tumor other than medulloblastoma or PNET in the posterior fossa, for
example, patients with diagnosis of Atypical Teratoid / Rhabdoid Tumor (ATRT),
supratentorial PNET, pineoblastoma, ependymoblastoma, ETANTR are excluded.
• Research participants with other clinically significant medical disorders that could
compromise their ability to tolerate protocol therapy or would interfere with the
study procedures or results history.
Participants in the Stratum S maintenance chemotherapy portion of the study must meet the
criteria below prior to start of vismodegib therapy:
• Participants must be Stratum S (SHH)
• Participants must be skeletally mature defined as females with a bone age ≥ 15 years
and males with a bone age ≥ 17 years.
• Must be able to swallow pills
• BSA must be >0.67 and <2.5 m2
• Male and female participants of reproductive potential must agree to effective
contraception during and after study treatment. See Appendices I and II for further
guidance for participants receiving vismodegib
• ANC ≥ 1000/mm^3 (after G-CSF discontinued)
• Platelets ≥ 50,000/mm^3 (without support)
• Hgb ≥ 8 g/dL (with or without transfusion support)
• Serum creatinine ≤ 1.5 mg/dL
• Total bilirubin ≤ 1.5X the institutional ULN
• SGPT (ALT) ≤ 2.5X the institutional ULN
• SGOT (AST) ≤ 2.5X the institutional ULN
• Alkaline Phosphatase ≤ 1.5X the institutional ULN
• Serum albumin ≥ 2.5 g/dL
Participants in the exercise intervention portion of the study must meet all criteria
below:
• Must be ≥ 5 years and < 22 years at the time of enrollment
• Must have no congenital heart disease
• Must be capable of performing the exercise intervention at the time of baseline
assessment as determined by the treating physician.
Participants in the cognitive remediation intervention portion of the study must meet all
criteria below:
• Completed protocol-directed radiation therapy
• ≥5 years at the time of remediation intervention consent or age is greater than or
equal to 22 years and less than 40 years and patient has SHH medulloblastoma
• English as primary language and training aide who speaks English available to
participate in required sessions
• No significant cognitive impairment operationalized as either an IQ < 70 for children
with St. Jude SJMB12 study baseline testing or based on clinician judgment baseline IQ
missing
• No major sensory or motor impairment that would preclude valid cognitive testing
(e.g., unresolved posterior fossa syndrome, blindness, poorly controlled
seizures/photosensitive epilepsy, psychosis) or a major psychological condition that
would preclude completion of the intervention (e.g., significant oppositionality,
autism spectrum disorder, severe anxiety or depressive symptoms)
Radiation: Craniospinal Irradiation with boost to the primary tumor site, Drug: Cyclophosphamide, Drug: Cisplatin, Drug: Vincristine, Drug: Vismodegib, Drug: Pemetrexed, Drug: Gemcitabine, Other: Aerobic Training, Other: Neurocognitive Remediation
Medulloblastoma, Brain and Nervous System
SJMB12, Brain Cancer, Brain Tumors in Children, Cisplatin, Cyclophosphamide, Embryonal Tumors of CNS, GDC-0449, Gemcitabine, Hedgehog Pathway Inhibitor, Infratentorial, Mass in Brain, Medulloblastoma, Medulloblastoma Brain Tumor, Medulloblastoma Tumor, Molecular, Neuroectodermal Tumor, Primitive, Newly Diagnosed Childhood Medulloblastoma, Non-SHH Non-WNT, Pediatric Brain Tumor, Pemetrexed, Posterior Fossa Tumor, Proton Beam Therapy, Radiation Therapy, Rare Brain Tumor, Risk, SHH, Sonic Hedgehog Pathway, St Jude Medullo, St. Jude Brain Tumor Studies, St. Jude Medullo, St. Jude Studies, St. Jude Treatment, Treatment for Brain Tumors in Children, Untreated Childhood Medulloblastoma, Vincristine, Vismodegib, WNT
Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE)
This project is a multicenter, randomized, placebo-controlled, double-blind clinical trial
that is designed to test whether treating patients who are at risk for development of lupus
with hydroxychloroquine can slow accumulation of disease features. Effects on clinical
progression of symptoms, patient-reported outcomes and changes in the immune markers of
response will be measured and toxicity of the treatment will be assessed. This trial is a
first step in testing a prevention strategy for lupus.
Call 214-648-5005 studyfinder@utsouthwestern.edu
David Karp
13762
All
15 Years to 49 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03030118
STU 112015-016
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Between 15 and 49 years of age, inclusive, at Visit 1.
2. Anti-nuclear antibody (ANA) titer of 1:80, or greater, as determined by
immunofluorescence assay (IFA).
3. Participants must have at least one (but not three or more) additional clinical or
laboratory criterion from the 2012 Systemic Lupus International Collaborating Clinics
(SLICC) classification criteria.
4. Written informed consent (and assent when applicable) obtained from subject or
subject's legal representative and ability for subject to comply with the requirements
of the study.
Exclusion Criteria:
1. The subject meets the 2012 SLICC classification criteria for SLE at Visit 1 (i.e., ANA
plus 3 other criteria, or ANA plus biopsy-proven lupus nephritis).
2. The subject has been diagnosed with another autoimmune disorder, other than autoimmune
thyroid conditions.
3. The subject has fibromyalgia, based on clinical history and exam.
4. The subject has previously been or is currently being treated with oral antimalarial
agents including hydroxychloroquine, chloroquine, or quinacrine.
5. The subject is currently or has been treated with immunosuppressive, immune modifying,
or cytotoxic medications as listed in Section 7.2.
6. Use of any investigational agent within the preceding 12 months.
7. History of primary immunodeficiency.
8. Active bacterial, viral, fungal, or opportunistic infection.
9. Evidence of infection with human immunodeficiency virus (HIV), Hepatitis B, or
Hepatitis C.
10. Concomitant malignancy or history of malignancy with the exception of adequately
treated basal or squamous cell carcinoma of the skin, or carcinoma in situ of the
cervix.
11. The subject has significant findings on ophthalmological examination that, in the
opinion of the examining Ophthalmologist, prevent safe use of hydroxychloroquine.
12. The subject has other contraindications to treatment with hydroxychloroquine including
pre-existing ocular disease, hepatic impairment, psoriasis, porphyria, or allergy to
the drug or class.
13. Co-morbidities requiring systemic corticosteroid therapy greater than 10 mg of
prednisone per day, or equivalent, or a change in corticosteroid dose within the 3
months prior to Visit 1.
14. Starting, stopping, or changing the dose of over the counter or prescription
non-steroidal anti-inflammatory drugs (NSAIDs) in the three months prior to Visit 1.
15. Pregnant, breastfeeding, or unwilling to practice birth control during participation
in the study.
16. Presence of a condition or abnormality that in the opinion of the Investigator would
compromise the safety of the patient or the quality of the data.
17. Inability to comply with the study visit schedule and procedures.
Computer Training Program for Younger Patients With a Brain Tumor Who Underwent Radiation Therapy
This randomized clinical trial studies how well an adaptive computerized cognitive training
program works compared to a non-adaptive computerized cognitive training program in treating
younger patients with brain tumor who underwent radiation therapy. Providing a computer
training program may improve the well-being and quality of life of patients with cognitive
(physical and mental) function difficulties caused by radiation therapy to the brain.
• Patient must be newly diagnosed or relapsed/progressed with a brain tumor that has not
previously been treated with CRT
• Note: COG therapeutic study participation is not required for ACCL10P1 enrollment
• Patient enrollment must occur within 4 calendar months following completion of CRT
• Reminder: after patient enrollment, baseline testing followed by randomization
must occur within 2-4 months after completion of CRT
• The patient must have an identified caregiver who is willing and able to oversee the
training practice during the intervention period (ie, for 5-9 weeks starting
approximately 3 months after completion of CRT)
• The patient must have access to a telephone and phone number where they can be reached
• The patient and caregiver must have reading, speaking and listening comprehension of
English
• All patients and/or their parents or legal guardians must sign a written informed
consent (patient assent is also recommended when applicable according to each
institution's policy)
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with pontine glioma are not eligible
• Patients with an estimated survival of less than one year are not eligible
• Patients with a history of traumatic brain injury prior to tumor diagnosis are not
eligible
• Patients with a motor, visual, or auditory handicap that prevents computer use (e.g.,
unresolved posterior fossa syndrome) are not eligible to participate in this trial
• Patients with full-scale intelligence quotient (IQ) < 70 per previous testing OR
existing diagnosis of/educational classification as a student with an intellectual
disability are not eligible
Procedure: Cognitive Assessment, Other: Computer-Assisted Cognitive Training, Procedure: Psychosocial Assessment and Care, Other: Quality-of-Life Assessment, Other: Questionnaire Administration
Brain Neoplasm, Recurrent Brain Neoplasm, Brain and Nervous System
Primary Objective:
Long-term safety and pharmacokinetics (PK) of neoGAA
Secondary Objective:
Long-term effect of neo-GAA on pharmacodynamic and exploratory efficacy variables
Call 214-648-5005 studyfinder@utsouthwestern.edu
Jaya Trivedi
46764
All
Not specified
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT02032524
STU 012014-036
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Inclusion criteria:
Patients with Pompe disease who previously completed a neoGAA study. The patient and/or
their parent/legal guardian is willing and able to provide signed informed consent, and
the patient, if <18 years of age, is willing to provide assent if deemed able to do so.
The patient (and patient's legal guardian if patient is <18 years of age) must have the
ability to comply with the clinical protocol.
The patient, if female and of childbearing potential, must have a negative pregnancy test
[urine beta-human chorionic gonadotropin] at baseline.
Exclusion criteria:
The patient is concurrently participating in another clinical study using investigational
treatment.
The patient, in the opinion of the Investigator, is unable to adhere to the requirements
of the study.
The patient has clinically significant organic disease (with the exception of symptoms
relating to Pompe disease), including clinically significant cardiovascular, hepatic,
pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent
illness, or extenuating circumstance that, in the opinion of the Investigator, precludes
participation in the study or potentially decreases survival.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.