A Phase I Trial of Donor- Derived 19-28z CAR T Cells Following Allogeneic Transplant for the Treatment of CD19 Malignancies
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 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 |
Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg
|
Experimental: 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 |
Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg
|
Experimental: 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 |
Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg
|
Experimental: 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 |
Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) [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
Eligibility Criteria
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
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CLL
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High risk in any remission status as defined by 17p deletion or Richter's transformation, or
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All other patients eligible after at least 2 lines of standard or investigational chemotherapy
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B-NHL
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Refractory or stable disease to last line of therapy per ICML 2014. Patients should have at least 2 lines of prior therapy.
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Relapsed disease in patients who are not candidates for autologous transplant
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Patient's age is ≥ 18 and ≤ 60.
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KPS ≥ 70%
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Patients must have CD19 expression (by any detection method) demonstrated on their malignant cells at the time of enrollment on the protocol.
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Patients relapsed after prior CD19 CAR T cell or blinatumomab are eligible for enrollment as long as CD19 expression is still prese on the malignant cells.
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Patients who have a matched related donor willing to donate HSC for allograft and PBMC for CAR T cell generation
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Patients must have adequate organ function measured by:
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Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50%
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Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
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Renal: serum creatinine <1.3 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60 ml/min (measured or calculated/estimated)
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Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
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Negative serum pregnancy test for women of child-bearing potential is required
Exclusion Criteria:
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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.
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Patients who have undergone a prior allogeneic or autologous stem cell transplant within the previous six months.
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Pregnant or breast feeding
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HIV infection
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Progressive disease at time of transplant
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Patients with known autoimmune disease.
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Patients with active or clinically significant neurological disorders, such as seizure disorders.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
Investigators
- Principal Investigator: Miguel-Angel Perales, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 17-331