This study is designed to evaluate the safety and effectiveness of CART123 cells either alone or when combined with ruxolitinib in pediatric and young adult subjects with relapsed or refractory AML. Subjects will be enrolled into one of two treatment cohorts: subjects who will receive CART123 alone (Cohort A) or subjects who will receive CART123 in combination with ruxolitinib (Cohort B).
This trial will be conducted at the Children's Hospital of Philadelphia with CART123 infusions occurring in an outpatient setting with close follow-up. Approximately 18 subjects will be treated on Cohort A and 12 patients treated on Cohort B. Cohort A will consist of a dose escalation of CART123 cells administered intravenously on Day 0 after lymphodepleting chemotherapy. . Cohort B will consist of a fixed dose of CART123 cells (2x106 CART123 cells/kg) to be administered intravenously on Day 0 in combination with age and BSA-based dosing of ruxolitinib given orally from the start of lymphodepleting chemotherapy until Day -2 and again from Day+7 to Day+13. There is no dose escalation of CART123 cells or ruxolitinib on this cohort, but a dose de-escalation of ruxolitinib is planned in the event of unacceptable toxicity defined by dose de-escalation rules.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
CART123 cells: lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains.
Ruxolitinib: an orally administered janus-activated kinase (JAK) inhibitor that selectively inhibits JAK1 and JAK2.
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Evaluate the Safety of CART123
Frequency of Adverse events will be measured by evaluating the frequency and severity of treatment related adverse events following administration of CART123
Time frame: 5 years
Safety of CART123 in combination with Ruxolitinib
Frequency of Adverse events will be measured by evaluating the frequency and severity of treatment related adverse events following administration of CART123 and Ruxolitinib
Time frame: 5 Years
Determine Maximum Tolerated Dose of CART123
The Maximum Tolerated Dose will be determined by measuring the incidence of dose limiting toxicities following administration of the CART123 product.
Time frame: 5 years
Determine Feasibility of CART123 Treatment
Measured by the proportion of enrolled subjects who receive CART123 infusion.
Time frame: 5 years
Determine feasibility of combination treatment with CART123 and ruxolitinib
Measured by the rate of enrolled subjects who receive CART123 infusion and at least 7 days of ruxolitinib.
Time frame: 5 years
Determine the Preliminary Efficacy of CART123
Measured by the rate of subjects who achieve complete remission following treatment with CART123 at Day 28.
Time frame: 5 years
Determine the Preliminary Efficacy of CART123 + Ruxolitinib
Measured by the rate of subjects who achieve complete remission following treatment with CART123 and at least 7 days of Ruxolitinib at Day 28.
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Time frame: 5 years
Evaluate the need for rescue stem cell transplant following treatment with CART123 or CART123 with Ruxolitinib
Determine the proportion of infused subjects who proceed to allogeneic HSCT for bone marrow aplasia following treatment with CART123 or CART123 with Ruxolitinib
Time frame: 5 years