Autologous T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
The purpose of this study is to test the safety of giving the patient special cells made from their own blood called "Modified T-cells". The goal is to find a safe dose of modified T-cells for patients whose leukemia has returned to the bone marrow.
Relapsed B-Cell Acute Lymphoblastic Leukemia
Procedure: leukapheresis or collection of PBMCs
Biological: modified T cells
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Autologous T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia|
- safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]of gene-modified autologous T cells targeted to CD19 and infused into patients with relapsed or refractory B- ALL. Toxicities that are related to treatment will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
- assess the persistence of modified T cells [ Time Frame: 1 year ] [ Designated as safety issue: No ]Gene-modified T cells will be measured as per Table II from peripheral blood, bone marrow and/or lymph nodes. The percentage of gene-modified T cells T cells will be calculated and summarized at each follow-up time point. The data will be plotted over time to describe the time trend of T cell persistence.
- the development of B cell aplasia [ Time Frame: 1 year ] [ Designated as safety issue: No ]B cell aplasia will be measured as a surrogate marker for 19-28z+ T cell efficacy. Serum levels of normal B cells from peripheral blood and bone marrow aspirates will be monitored by FACS. The mean cell concentrations will be summarized and plotted against time.
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||May 2016|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
Experimental: Collection Only Arm
Patients will undergo leukapheresis or collection of PBMCs from whole blood based on age and weight of the patient. PBMC collection may occur before or after re-induction chemotherapy depending patient's disease status and number of circulating peripheral blood lymphocytes. The preferred method of collection will be apheresis, however, in cases where apheresis is not possible patients will donate whole blood for T-cell isolation. The product will be frozen and stored until the patient has completed all pertinent pre-treatments and qualifies for treatment
|Procedure: leukapheresis or collection of PBMCs|
Experimental: Treatment Arm with Gene-modified T cells
Patients will undergo leukapheresis or collection of PBMCs as noted above. While genetically modified T cells are generated patients may receive a re-induction/consolidation chemotherapy selected by the treating physician based on prior therapy, prior adverse reactions to chemotherapy, and highest likelihood to achieve an optimal response. Once a sufficient number of CAR-modified T cells are generated patient will be treated with conditioning chemotherapy and be infused with CAR-modified T cells over 2 days.
|Drug: cyclophosphamide Biological: modified T cells|
|Contact: Kevin Curran, MD||212-639-5836|
|Contact: Renier Brentjens, MD, PhD||212-639-7053|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Kevin Curran, MD 212-639-5836|
|Contact: Renier Brentjens, MD,PhD 212-639-7053|
|Principal Investigator: Kevin Curran, MD|
|Principal Investigator:||Kevin Curran, MD||Memorial Sloan-Kettering Cancer Center|