A Phase I Trial of T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
Overview
- Phase
- Phase 1
- Intervention
- leukapheresis or collection of PBMCs
- Conditions
- Relapsed B-Cell Acute Lymphoblastic Leukemia
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 23
- Locations
- 2
- Primary Endpoint
- safety
- Status
- Active, not recruiting
- Last Updated
- 11 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort 1 (MRD)
Patients with no morphologic evidence of disease at the time of T cell infusion, (\<5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Cohort 1 patients will receive conditioning chemotherapy followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of End of Production (EOP) T cells, under or over estimation of CAR modified T-cells may occur. Patients may receive an altered fractionation of the total doses (e.g. ½ on Day 0 and ½ on Day +1) or up to 35% over total cell dose with approval by the participating site PI. In both cohorts, patients will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion and did not experience any non-hematologic grade 4 toxicities.
Intervention: leukapheresis or collection of PBMCs
Cohort 1 (MRD)
Patients with no morphologic evidence of disease at the time of T cell infusion, (\<5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Cohort 1 patients will receive conditioning chemotherapy followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of End of Production (EOP) T cells, under or over estimation of CAR modified T-cells may occur. Patients may receive an altered fractionation of the total doses (e.g. ½ on Day 0 and ½ on Day +1) or up to 35% over total cell dose with approval by the participating site PI. In both cohorts, patients will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion and did not experience any non-hematologic grade 4 toxicities.
Intervention: cyclophosphamide based chemotherapy regimens
Cohort 1 (MRD)
Patients with no morphologic evidence of disease at the time of T cell infusion, (\<5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Cohort 1 patients will receive conditioning chemotherapy followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of End of Production (EOP) T cells, under or over estimation of CAR modified T-cells may occur. Patients may receive an altered fractionation of the total doses (e.g. ½ on Day 0 and ½ on Day +1) or up to 35% over total cell dose with approval by the participating site PI. In both cohorts, patients will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion and did not experience any non-hematologic grade 4 toxicities.
Intervention: modified T cells
Cohort 2 (Morphologic Disease)
Pts with morphologic evidence of disease at the time of T cell infusion, (≥5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Pts with increased blasts (5-10% blasts) that are immunophenotypically consistent with recovering marrow from prior re-induction chemo may be treated under Cohort 1 with approval of the participating site PI. Cohort 2 pts will get conditioning chemo followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of EOP T cells, under or over estimation of CAR modified T-cells may occur. Pts may get up to 35% over total cell dose with approval by the participating site PI. Both cohorts, pts will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion \& did not experience any non-hematologic grade 4 toxicities.
Intervention: leukapheresis or collection of PBMCs
Cohort 2 (Morphologic Disease)
Pts with morphologic evidence of disease at the time of T cell infusion, (≥5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Pts with increased blasts (5-10% blasts) that are immunophenotypically consistent with recovering marrow from prior re-induction chemo may be treated under Cohort 1 with approval of the participating site PI. Cohort 2 pts will get conditioning chemo followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of EOP T cells, under or over estimation of CAR modified T-cells may occur. Pts may get up to 35% over total cell dose with approval by the participating site PI. Both cohorts, pts will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion \& did not experience any non-hematologic grade 4 toxicities.
Intervention: cyclophosphamide based chemotherapy regimens
Cohort 2 (Morphologic Disease)
Pts with morphologic evidence of disease at the time of T cell infusion, (≥5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Pts with increased blasts (5-10% blasts) that are immunophenotypically consistent with recovering marrow from prior re-induction chemo may be treated under Cohort 1 with approval of the participating site PI. Cohort 2 pts will get conditioning chemo followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of EOP T cells, under or over estimation of CAR modified T-cells may occur. Pts may get up to 35% over total cell dose with approval by the participating site PI. Both cohorts, pts will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion \& did not experience any non-hematologic grade 4 toxicities.
Intervention: modified T cells
Outcomes
Primary Outcomes
safety
Time Frame: 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 Outcomes
- assess the persistence of modified T cells(1 year)
- the development of B cell aplasia(1 year)