Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory AML as a Bridge to Allogeneic Stem Cell Transplant
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.
• ≥ 12 years old at the time of informed consent
• Ability to provide written informed consent and HIPAA authorization.
• 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 above 5%) but evidence of efficacy exists, a second cycle without interruption will be given with the goal of achieving morphologic remission and repeat BM biopsy on days 21-28 of this cycle. If residual disease or disease progression is captured, then they will be considered refractory and will qualify for this trial. This is unless the patient now qualifies for a more intensive induction therapy that they did not qualify for when aza/ven was initially chosen as first-line treatment. Given the low response rate for aza/ven in the RR-AML, CR of only 13%, this combination would not be a prerequisite to qualify for the study.
• If these patients who fail first line treatment have an FDA approved treatment options available (including targeted and non-targeted treatment) for a second line treatment, they do not qualify for the trial until they also are deemed nonresponsive to those. If an approved second line is not available, patients will be eligible after first line failure.
• Creatinine clearance of \> 60ml/min (or otherwise non clinically significant, per study investigator)
• alanine aminotransferase/ aspartate aminotransferase ALT/AST \< 3 x ULN
• Bilirubin \< 2 x ULN (UPPER LIMIT OF NORMAL)
• Pulmonary Function Test (PFT) with a DIFFUSE LUNG CAPACITY , DLCO, of ≥ 60% (if not completed within 6 months from Day 0)
• Adequate echocardiogram with EJECTION FRACTION, EF, of ≥50%
⁃ Adequate venous access for apheresis and no other contraindications for leukapheresis
⁃ Confirmation of a bone marrow donor for post CD4CAR transplant to proceed to transplant if eligible post treatment.