A study to assess the efficacy and safety of JCAR017, a CAR-T cell therapy, in pediatric subjects with relapsed or refractory CD19+ B-Cell Acute Lymphoblastic Leukemia and B-Cell Non-Hodgkin Lymphoma.
- Conditions
- Relapsed or refractory (r/r) CD19+ B-Cell Acute Lymphoblastic Leukemia (B-ALL) and B-Cell Non-Hodgkin Lymphoma (B-NHL).MedDRA version: 20.0Level: LLTClassification code 10029593Term: Non-Hodgkin's lymphoma NOSSystem Organ Class: 100000004864MedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disordersMedDRA version: 20.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-001246-34-ES
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 111
1. Phase 1b: Subject < 18 years of age and weighs = 12 kg (for subjects receiving a dose of 0.5x10^6 JCAR017 CAR+ T cells/kg) or = 6 kg (for subjects receiving a dose of 1x10^6 JCAR017 CAR+ T cells/kg) at the time of signing the informed consent form (ICF)/informed assent form (IAF).
Phase 2: Subject = 25 years of age and weighs = 12 kg (if RP2D is 0.5 x 10^6 JCAR017 CAR+ T cells/kg) or = 6 kg (if RP2D is 1 x 10^6 JCAR017 CAR+ T cells/kg) at the time of signing the ICF/IAF.
2. Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Investigator considers the subject is appropriate for adoptive T cell therapy.
5. Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy)
6. Subject has a Karnofsky score of = 50 (subjects = 16 years of age) or a Lansky score = 50 (subjects < 16 years of age).
7. Phase 1b: Subjects with r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either of the following:
First or greater marrow relapse, or
Any marrow relapse after allogeneic HSCT, or
Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
Ineligible for allogeneic HSCT
Note: Subjects will be included regardless of MRD status.
Phase 2: Subjects with one of the following:
Cohort 1: r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either:
First or greater marrow relapse, or
Any marrow relapse after allogeneic HSCT, or
Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
Ineligible for allogeneic HSCT.
Cohort 2: MRD+ B-ALL, defined as:
< 5% lymphoblasts by morphology
MRD detected by a validated assay at a frequency of 1 x10-4 or greater in BM cells after two lines of therapy.
Cohort 3: r/r B-NHL, defined as measurable disease after 1 or more lines of chemotherapy and/or having failed HSCT or being ineligible for HSCT.
8. Subjects with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed one or more lines of tyrosine-kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated.
9. Adequate organ function, defined as:
Adequate BM function to receive LD chemotherapy as assessed by the Investigator.
Subject with adequate renal function, which is defined as:
Creatinine clearance calculated using the Schwartz formula, (Schwartz, 1976) or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m2.
Alanine aminotransferase (ALT) = 5 x upper limit of normal (ULN) and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert’s syndrome or
lymphomatous infiltration of the liver).
Adequate pulmonary function, defined as = Grade 1 dyspnea according to Common Toxicity Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) = 92% on room air.
Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) = 4
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment.
5. Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy.
6. Prior CAR T cell or other genetically-modified T cell therapy.
7. Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion.
9. Subject has presence of acute or chronic graft-versus-host disease (GVHD).
10. Subject with active autoimmune disease requiring immunosuppressive therapy.
11. Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months.
12. Subject with a concomitant genetic syndrome, with the exception of Down’s syndrome.
13. Subject with active CNS disease and significant neurological deterioration. Subjects with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not have significant neurological deterioration and, in the opinion of the study investigator, the CNS disease burden can be controlled until JCAR017 infusion.
14. Subject with a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis.
15. Subject is pregnant or nursing.
16. Subject has used the following:
Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide = 300 mg/m2) given after leukapheresis to maintain disease control must be stopped = 7 days prior to LD chemotherapy.
Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week prior to leukapheresis. Oral anticancer agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 2 weeks prior to leukapheresis.
Experimental agents within 4 weeks prior to leukapheresis unless no response or PD is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis.
Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as antitumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R).
Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion.
Radiation within 6 weeks
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method