Phase 1 Trial of Autologous CD123-Directed CAR T-Cells (CART123) as Monotherapy or in Combination With Ruxolitinib in Relapsed/Refractory Acute Myeloid Leukemia
Stephan Grupp MD PhD
Summary
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).
Description
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 lymphode…
Eligibility
- Age range
- 0–29 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 1\. Age at time of consent: Cohort A: 0-29 years. Cohort B: 1-29 years (Note: the first subject at each dose level of Cohort B must be ≥12 years old) * 2\. Subjects with AML in second or greater relapse, post-transplant relapse, or with chemotherapy-refractory disease. Specifically: 1. Second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR 2. Any detectable disease post-allogeneic transplant with flow cytometric confirmation of myeloid leukemia of at least 0.1%; OR 3. Re…
Interventions
- BiologicalAnti-CD123 LV redirected T cells (CART123)
CART123 cells: lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains.
- DrugRuxolitinib (JAKAVI®)
Ruxolitinib: an orally administered janus-activated kinase (JAK) inhibitor that selectively inhibits JAK1 and JAK2.
Location
- Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania