Relapsed B-Cell Acute Lymphoblastic Leukemia
Conditions
Keywords
T cell Immunotherapy, CD19 Targeted Therapy, Chimeric Antigen Receptor (CAR) Modified T cells, Conditioning Chemotherapy, 13-052
Brief summary
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.
Detailed description
This is a phase I multicenter clinical trial for pediatric and young adult patients with relapsed/refractory CD19+ B-ALL. The T cell doses originally proposed in this study were based on doses administered safely in prior T cell adoptive therapy trials, but the dose has been modified based on the toxicities observed in adult patients with morphologic evidence of relapsed B-ALL treated on MSKCC IRB 09-114.
Interventions
PROCEDUREleukapheresis or collection of PBMCs
DRUGcyclophosphamide based chemotherapy regimens
BIOLOGICALmodified T cells
Sponsors
Memorial Sloan Kettering Cancer Center
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 26 Years
Healthy volunteers
No
Inclusion criteria
for Collection Arm of the protocol: Age \< 26 years, whose disease meets one of the following 3 criteria: * VHR\* * Patients in 1st or subsequent marrow relapse (isolated or combined), at the time of relapse, during retrieval therapy, or after achievement of CR. * Refractory disease \*Definitions of VHR B-ALL include the following: * NCI HR-ALL and age ≥ 13 years at diagnosis * CNS-3 leukemia at diagnosis * Day 29/End of Induction BM MRD \> 0.01% * Induction failure (M3 BM at Day 29/End of Induction) * Hypodiploidy (n\< 44 chromosomes and/or a DNA index \< 0.81) * t(9;22) ALL (Philadelphia Chromosome/Ph+ ALL) * t(17;19) ALL or Ph-Like ALL * MLL gene rearrangement * IKZF1 deletions * Intrachromosomal amplification of chromosome 21 (iAMP21) Please note patients that only meet the criteria for collection/storage of PBMCs will need to be reconsented prior to infusion of genetically modified T-cells. Inclusion Criteria for Treatment Arm of this protocol: * Patients must have a history of relapsed/refractory CD19+ B-ALL involving the marrow to be eligible for infusion of modified T cells. * Please note ≥5% blasts by morphology, FISH/cytogenetics, molecular translocation and/or flow cytometry constitutes a bone marrow relapse on this protocol. Patients must also fulfill one of the following criteria to be eligible for infusion of modified T cells: * Second or greater (≥2) relapse * Early first marrow relapse (1st CR \<18 months) * Intermediate/Late first marrow relapse (1st CR \>18 months) with poor initial response (≥5% blasts by morphology and/or flow cytometry) following reinduction chemotherapy * Refractory Disease * Ineligible for HSCT as determined by the treating physician in consultation with the BMT service * Patient would not benefit from additional chemotherapy as determined by the treating physician * KPS or Lansky score ≥ 60 * Pulmonary function (measured prior to conditioning chemotherapy): o \> 90% oxygen saturation on room air by pulse oximetry. * Renal Function (measured prior to conditioning chemotherapy): o Serum creatinine ≤2.0mg/dL for patients over 18 years or ≤2.5 x institutional ULN for age * Hepatic Function (measured prior to conditioning chemotherapy): * AST ≤ 5 x the institutional ULN. Elevation secondary to leukemic involvement is not an exclusion criterion. Leukemic involvement will be determined by the presence of progressive relapse defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of know hepatotoxic medication (e.g. azoles). * Total bilirubin ≤ 2.5 x the institutional ULN
Exclusion criteria
for Collection of T cells/PBMCs: * Karnofsky/Lansky performance status \<60. * Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation * Patients with active HIV, hepatitis B or hepatitis C infection. * Females who are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| safety | 1 year | of gene-modified autologous T cells targeted to CD19 and infused into patients with relapsed/refractory B- ALL. Toxicities 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. Adverse Events/Toxicities will be graded/attributed starting at time of T cell infusion and continue for up to 30 days or until modified T cells are no longer present. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| assess the persistence of modified T cells | 1 year | 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 | 1 year | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKevin Curran, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed