A Phase I Trial Evaluating the Safety of Consolidative Infusions of CD19-Specific Chimeric Antigen Receptor (CAR) T Cells Following T-cell Depleted Allogeneic Transplantation for High Risk B-cell Malignancies
Overview
- Phase
- Phase 1
- Intervention
- CAR T-Cell Infusion
- Conditions
- Leukemia
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD)
- Status
- Withdrawn
- Last Updated
- 11 months ago
Overview
Brief Summary
The purposed of this study is to determine whether an infusion with specialized 'modified T cells' (or CD19 chimeric antigen T cells, also called CD19 CAR T cells) that target the B cell marker will reduce the risk of relapse after transplant.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The following criteria must be met prior to the allogenic transplantation:
- •ALL in second remission or greater (≥ CR2)
- •Please refer to section 3.0 for more discussion of ALL in CR1 versus CR2
- •High risk in any remission status as defined by 17p deletion or Richter's transformation, or
- •All other patients eligible after at least 2 lines of standard or investigational chemotherapy
- •Refractory or stable disease to last line of therapy per ICML
- •Patients should have at least 2 lines of prior therapy.
- •Relapsed disease in patients who are not candidates for autologous transplant
- •Patient's age is ≥ 18 and ≤
- •Patients must have CD19 expression (by any detection method) demonstrated on their malignant cells at the time of enrollment on the protocol.
Exclusion Criteria
- •Active and uncontrolled infection at time of transplantation. Please note that patients being actively treated for a viral reactivation may be enrolled on the protocol at the discretion of the investigators.
- •Patients who have undergone a prior allogeneic or autologous stem cell transplant within the previous six months.
- •Pregnant or breast feeding
- •HIV infection
- •Progressive disease at time of transplant
- •Patients with known autoimmune disease.
- •Patients with active or clinically significant neurological disorders, such as seizure disorders.
Arms & Interventions
Cohort -1
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 1 x 10\^4 cells/kg
Intervention: CAR T-Cell Infusion
Cohort 1
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 1 x 10\^5 cells/kg
Intervention: CAR T-Cell Infusion
Cohort II
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 2 x 10\^5 cells/kg
Intervention: CAR T-Cell Infusion
Cohort III
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 4 x 10\^5 cells/kg
Intervention: CAR T-Cell Infusion
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD)
Time Frame: 24 month
To determine maximum tolerated dose (MTD) of intravenously administered allogeneic, donor-derived 19-28z CAR T cells administered following TCD allo-HSCT for patients with high-risk CD19+ malignancies