B-cell Acute Lymphoblastic Leukemia (ALL) MedDRA version: 19.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: JCAR015
Product Code: JCAR015
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Autologous CD3+ T Cells Expressing CD19 C
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A Inclusion Criteria common to all cohorts: 1. Age =18 years at the time of signing the informed consent form 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements 4. Diagnosis of B-cell ALL 5. Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy) 6. Eastern Cooperative Oncology Group (ECOG) performance status = 2 7. No contraindications to cyclophosphamide. This includes subjects with: · hypersensitivity to cyclophosphamide, any of its metabolites · acute infections · bone marrow aplasia or bone marrow depression prior to treatment · urinary tract infection · acute urothelial toxicity from cytotoxic chemotherapy or radiation therapy · urinary outflow obstruction · obstruction 8. Adequate organ function, defined as: a. Serum creatinine = 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance (Cockcroft and Gault, see Appendix D) > 30 mL/min/1.73 m2 b. Alanine aminotransferase (ALT) = 5 × ULN and direct bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with leukemic infiltration of the liver) c. Adequate pulmonary function, defined as = Grade 1 dyspnea and oxygen saturation (SaO2) = 92% on room air d. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) = 40% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA) performed within 1 month of signing the informed consent form 9. Adequate central or peripheral vascular access for leukapheresis procedure. For subjects requiring central venous catheter (CVC) placement, a surgical consultation indicating subject eligibility for CVC placement is sufficient for enrolment. 10. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals without recipient knowledge about exposure to a genetically modified organ by the donor and having been informed about the potential risks associated with it at any point after receiving JCAR015 infusion. 11. Females of childbearing potential (FCBP) must: a. Have two negative pregnancy tests as verified by the Investigator (one negative serum beta human chorionic gonadotropin (ß-hCG) pregnancy test result within 7 days prior to the first dose of cytoreductive chemotherapy, and one negative serum or urine pregnancy test at the Part B screening evaluation prior to first JCAR015 infusion). She must agree to have another pregnancy test 90 days post final JCAR015 dose. This applies even if the subjec
Exclusion criteria
Exclusion criteria: Part A 1. Isolated extramedullary disease relapse 2. Concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome 3. Burkitt's lymphoma/leukemia or chronic myelogenous leukemia (CML) lymphoid blast crisis (p210 BCR-ABL+) 4. Prior malignancy, unless treated with curative intent and with no evidence of active disease present for > 5 years before signing the informed consent form, with the following exceptions: a. Subjects with Stage I breast cancer that has been completely and successfully treated, requiring no therapy or only anti-hormonal therapy b. Subjects with T1N0M0 or T2N0M0 colorectal cancer who have been completely and successfully resected and who are disease-free for > 2 years prior to screening c. Subjects with indolent prostate cancer, defined as clinical stage T1 or T2a, Gleason score = 6, and prostate-specific antigen (PSA) < 10 ng/mL, requiring no therapy or only anti- hormonal therapy d. Subjects with a history of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, fully resected, and with no evidence of active disease 5. Treatment with any prior gene therapy product 6. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of signing the informed consent form 7. Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) at the time of signing the informed consent form 8. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of signing the informed consent form 9. Active CNS involvement by malignancy, defined as CNS-3 per NCCN guidelines. Subjects with a history of CNS disease that has been effectively treated (defined as one documented negative CSF evaluation within 1 month prior to signing the informed consent form) will be eligible 10. History of any one of the following cardiovascular conditions within the past 6 months of signing the informed consent form: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease 11. History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis 12. Participation in an investigational research study using an investigational agent within 30 days of signing the informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohorts 1 – 4: To evaluate the efficacy of JCAR015 as measured by overall remission rate (ORR) after the final JCAR015 infusion in subjects with morphologic evidence of disease, based on independent review committee (IRC) assessment Cohort 5: To evaluate the safety and efficacy of JCAR015 in subjects with Minimal Residual Disease (MRD) ; Timepoint(s) of evaluation of this end point: Cohorts 1 – 4: ORR: up to 6 months post final JCAR015 infusion Cohort 5: MRD negative rate: : 90 days post the final JCAR015 infusion ; Secondary Objective: - To determine the safety and feasibility of administering JCAR015 in adult B-cell ALL subjects with relapsed/refractory disease. - To determine the safety and feasibility of administering JCAR015 in adult B-cell ALL subjects with minimal residual disease. - To evaluate disease control following administration of JCAR015 in adult B-cell ALL subjects with MRD. - To evaluate the percentage of subjects who achieve a complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) with no evidence of MRD in the bone marrow. - To characterize the cellular pharmacokinetic (PK) profile of JCAR015, including the quantity and persistence in the peripheral blood and bone marrow. - To evaluate the percentage of subjects who achieve a morphologic remission within 6 months after the final JCAR015 infusion and then proceed to hematopoietic stem cell transplantation (HSCT). ; Primary end point(s): Cohorts 1 – 4: Efficacy: ORR, defined as the proportion of subjects with CR or CRi as | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: AE assessment: up to 24 months post the final JCAR015 infusion Efficacy: up to 24 months post the final JCAR015 infusion Depth of MRD response: 90 days post the final JCAR015 infusion Feasibility: From initiation of Part A until subject withdraws, discontinues or completes study Biomarker: up to 24 months post the final JCAR015 infusion ; Secondary end point(s): Safety: Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities Efficacy: Efficacy: - Time from MRD response until MRD recurrence, morphologic relapse, or death - Relapse-free survival (RFS), defined as the time from achievement of CR or CRi, whichever occurs first, to relapse or death due to any cause - Event-free survival (EFS), defined as the time from the date of the first JCAR015 infusion to death from any cause, relapse, or treatment failure, whichever occurs first - Overall survival (OS), defined as the time from the date of the first JCAR015 infusion to date of death due to any reason - Percentage of subjects who achieve CR or CRi with an MRD-negative bone marrow, as assessed by IgH gene sequencing (or BCR-ABL qPCR or flow cytometry for Philadelphia chromosome-positive [Ph+] ALL subjects) - Depth of MRD response at 90 days after the last infusion of JCAR015. subjects) Feasibility: Proportion of subjects that have undergone leukapheresis who receive infusion of JCAR015 Biomarker: - Cellular PK profile of JCAR015 (eg, Cmax, Tmax, AUC) - Maximum expansion of JCAR015 as defined by | — |
Countries
Belgium, Germany, Italy, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed