Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).
Name: CART123 cells; cyclophosphamide; fludarabine
Description: Occurrence of adverse events that are possibly, probably, or definitely related to CART123 cells
Measure: Safety of CART123 in AML subjects Time: 5 YearsDescription: Percentage of manufacturing products that meet release criteria
Measure: Manufacturing feasibility Time: 5 YearsDescription: Overall Response Rate (ORR) at 28 +/- 5 days Standard morphologic complete response criteria (malignant blasts < 5% with count recovery) Malignant blasts < 5% without count recovery, and Minimal residual disease assessment
Measure: Efficacy of CART123 cells in AML subjects evaluated by ORR at Day 28 using standard clinical criteria Time: 15 YearsDescription: Reduction of blast count in the peripheral blood and marrow using standard clinical criteria (CBC with differential count, marrow aspirate with differential count) and flow cytometry
Measure: Efficacy of CART123 cells in AML subjects evaluated by reduction of blast count in the peripheral blood and marrow using standard clinical criteria and flow cytometry Time: 15 YearsDescription: Overall survival (OS) and progression-free survival (PFS) and cause(s) of death for all subjects a. PFS will be followed until the time of first relapse or receipt of additional therapy, excluding alloHCT for marrow aplasia.
Measure: Overall survival (OS) and progression-free survival (PFS) Time: 15 YearsDescription: Time between date of when the response criteria of CR/CRi was met to the date of relapse
Measure: Duration of response (DOR) Time: 15 YearsDescription: Percentage of subjects proceeding to alloHCT (or second allogeneic HCT)
Measure: Need for rescue alloHCT Time: 15 YearsDescription: The duration of in vivo survival of CART123 cells ("persistence") is defined as the period of time above the limit of detection of Q-PCR for peripheral blood CART123 transgene sequences and/or flow cytometry for scFv surface expression.
Measure: Determine persistence and trafficking of CART123 cells Time: 15 YearsAllocation: N/A
Single Group Assignment
There is one SNP
Patients with somatic JAK2 V617F mutation by PCR or next generation sequencing. --- V617F ---