Study of Anti-CD33 Chimeric Antigen Receptor-Expressing T Cells (CD33CART) in Children and Young Adults With Relapsed/Refractory Acute Myeloid Leukemia
- Conditions
- Acute Myelogenous Leukemia
- Interventions
- Biological: CD33CART allogeneicBiological: CD33CART autologous
- Registration Number
- NCT03971799
- Brief Summary
This phase 1/2 trial aims to determine the safety and feasibility of antiCD33 chimeric antigen receptor (CAR) expressing T cells (CD33CART) in children and adolescents/young adults (AYAs) with relapsed/refractory acute myeloid leukemia (AML). The trial will be done in two phases: Phase 1 will determine the maximum tolerated dose of CD33CART cells using a 3+3 trial design, with dose-escalation for autologous products separated from dose-escalation for an allogeneic arm. Phase 2 is an expansion phase designed to evaluate the rate of response to CD33CART.
- Detailed Description
This study consists of two phases. The objectives of Phase 1 and Phase 2 are:
Phase 1:
Autologous Arm: To determine the maximum tolerated dose of lentivirally transduced autologous CD33-redirected CAR-T cells (CD33CART) in children and young adults with relapsed/refractory AML
Allogeneic Arm: To determine the maximum tolerated dose of lentivirally transduced allogeneic CD33-redirected CAR-T cells (ALLO-CD33CART) in children and young adults with post-HSCT relapsed/refractory AML
Phase 2:
To determine the percentage of recipients treated with CD33CART who achieve morphologic remission (\<5% blasts in marrow) at Day 28 post-CD33CART cell infusion
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 52
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CD33 CART allogeneic CD33CART allogeneic Patients who receive an allogeneic CD33CART cell infusion CD33CART autologous CD33CART autologous Patients who receive an autologous CD33CART cell infusion
- Primary Outcome Measures
Name Time Method Morphologic remission Day 28 post CD33CART infusion To determine the percentage of recipients treated with CD33CART who achieve morphologic remission (\<5% blasts in marrow) at Day 28 post-CD33CART cell infusion
Maximum tolerated dose - Autologous Arm Day 28 post CD33CART infusion To determine the maximum tolerated dose of lentivirally-transduced autologous CD33-redirected CAR-T cells (CD33CART) in children and young adults with relapsed/refractory AML
Maximum tolerated dose - Allogeneic Arm Day 28 post CD33CART infusion To determine the maximum tolerated dose of lentivirally-transduced allogeneic CD33-redirected CAR-T cells (ALLO-CD33CART) in children and young adults with post-HSCT relapsed/refractory AML
- Secondary Outcome Measures
Name Time Method Feasibility of CD33CART infusion 6 weeks post apheresis To determine the feasibility of infusing CD33CART in recipients with AML
Molecular Cytokine release syndrome (CRS), sinusoidal occlusion syndrome (SOS), or other CD33CART related toxicities 8 weeks post CD33CART infusion To determine the incidence and severity of cytokine release syndrome (CRS), sinusoidal occlusion syndrome (SOS), or other CD33CART related toxicities
Overall survival, event-free survival and treatment-related mortality 28 days post CD33CART infusion To estimate the overall survival, event-free survival, and treatment-related mortality at Day 28 post-CD33CART
GVHD 30 days post CD33CART infusion To determine the incidence and severity of acute graft-versus-host disease (GVHD) in patients treated on the allogeneic arm (ALLO-CD33CART).
Allogeneic hematopoietic stem cell transplantation 6 weeks post CD33CART infusion To determine the percentage of recipients able to proceed to allogeneic hematopoietic stem cell transplantation following treatment with CD33CART
Feasibility of CD33CART manufacture 2 weeks post start of CD33CART manufacture To determine the feasibility of manufacturing CD33CART for recipients with AML
Morphologic remission 28 days post CD33CART infusion To determine the percentage of recipients treated with CD33CART who achieve morphologic remission (\<5% blasts in marrow) at Day 28 post-CD33CART cell infusion (for those in Phase I)
MRD negativity 28 days post CD33CART infusion To determine minimal residual disease \[MRD\] negativity by flow cytometry (\<0.1%) at Day 28 post-CD33CART cell infusion
SOS and other post-transplant toxicities 6 weeks post HCT For treatment population that subsequently proceeds to HSCT: To determine the percentage of recipients able to proceed to allogeneic hematopoietic stem cell transplantation following treatment with CD33CART
Post-HCT time to engraftment 6 weeks post HCT For treatment population that subsequently proceeds to HSCT: To evaluate the post-HCT time to engraftment, transplant related mortality, incidence of acute and chronic graft-versus-host disease (aGVHD and cGVHD).
Molecular remission 28 days post CD33CART infusion To determine the percentage of recipients treated with CD33CART who achieve molecular remission (for those with an identified molecular marker) at Day 28 post-CD33CART cell infusion
Trial Locations
- Locations (6)
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Colorado
🇺🇸Aurora, Colorado, United States
National Cancer Institute - NIH
🇺🇸Bethesda, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Seattle Children's Hospital/Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States