Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory AML as a Bridge to Allogeneic Stem Cell Transplant
Huda Salman
Summary
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory AML. The study will evaluate safety in this patient population and also the presence of efficacy signal described by elimination of residual disease to qualify patients for stem cell transplant.
Description
The study will be performed as a dose-escalation protocol. The investigators expect to recruit 20 subjects at Indiana University with an expected dropout rate of 25% primarily due to rapid progression or death and screen and or manufacturing failure. Taking this into account, the investigators expect to treat 15 patients. The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR).…
Eligibility
- Age range
- 12+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. ≥ 12 years old at the time of informed consent 2. Ability to provide written informed consent and HIPAA authorization. 3. Diagnosis of AML that is CD4+ and must have failed standard induction/ first line treatment such as intensive induction or less intensive hypomethylation and venetoclax first line. In the specific case of azacitidine and venetoclax (aza/ven), BM biopsy for response assessment on days 21-28 of first cycle. If disease progression by increasing number of blasts is documented, patient will be eligible. If no morphologic remission (persistent BM blasts ab…
Interventions
- BiologicalCD4CAR
CD4CAR cells transduced with a lentiviral vector to express the single-chain variable fragment (scFv) nucleotide sequence of the anti-CD4 molecule derived from humanized monoclonal ibalizumab and the intracellular domains of CD28 and 4-1BB co-activators fused to the CD3ζ T-cell activation signaling domain administered by IV infusions as a single dose
Locations (4)
- University of Miami Sylvester Comprehensive Cancer CenterMiami, Florida
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, Indiana
- Riley Hospital for ChildrenIndianapolis, Indiana
- The University of Texas MD Anderson Cancer CenterHouston, Texas