CART-38 in Adult AML and MM Patients

Prior treatment

• Evidence of active hepatitis B or active hepatitis C. The following would not qualify as an active infection, thus would not exclude the subject from participating:
  • Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis for potential HBV reactivation.
  • Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment
• Patients < 3 months from prior autologous transplant or < 6 months from prior allo ASCT .
• Active acute or chronic GVHD requiring systemic therapy.
• Dependence on systemic steroids or immunosuppressant medications.

Other illness

• Any active, uncontrolled infection
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Active CNS disease. patients with a history of CNS involvement that was successfully treated are eligible. Additional CNS testing such as a lumbar puncture and/or brain imaging is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily equivalent of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Lab values

• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Other

• Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in this study.
• Patients with known somatic JAK2 V617F mutation by PCR or next generation sequencing.
• Pregnant or nursing (lactating) women.

• Male or female patients age ≥ 18 years.
• Patients must have one of the following diagnoses:
  • Cohort A: Acute Myeloid Leukemia (AML) which meets one of the following criteria: i. Patients with second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR ii. Patients with detectable disease post-allogeneic transplant with flow cytometric confirmation (MRD) of myeloid leukemia of at least 0.1%; OR iii. Patients with refractory disease defined as persistent bone marrow involvement with >5% blasts after two courses of induction chemotherapy for patients at initial presentation or >5% bone marrow blasts after one course of re-induction chemotherapy for patients who have relapsed after previously achieving a complete remission; OR iv. Patients with relapsed disease (defined as >5% bone marrow blasts after one course of standard chemotherapy) after previously achieving a complete remission. Note: Two cycles of combination therapy with a hypomethylating agent and venetoclax is considered one course of standard AML chemotherapy for the purpose of this criteria.
  • Cohort B: Relapsed/refractory multiple myeloma (MM) according to IMWG 2016 criteria which meets the following conditions: i. Relapsed/refractory disease after receiving ≥ 3 lines of therapy, to ensure the patient has been exposed to ≥ 1 IMiD®, ≥ 1 proteasome inhibitor, and daratumumab; where refractory MM is defined as the achievement of less than a partial response (< PR after ≥ 2 cycles) and relapsed MM requires patients be ≤ 12 months from the last dose of their prior treatment regimen to confirmation of relapse) AND ii. Patients must also have measurable disease as defined by one of the following:
• Serum M-protein ≥ 0.5 g/dL; 2. Urine M-protein ≥ 200 mg/24 hours; 3. Serum free light chain (FLC) assay; involved FLC level ≥ 100 mg/L provided the serum FLC ratio is abnormal; 4. ≥ 30% clonal plasma cells in the bone marrow aspirate or biopsy sample; 5. Measurable plasmacytomas > 2 cm in cross sectional diameter.
• AML only: Documentation of CD38 Expression on leukemic blasts by flow or by immunohistochemistry (IHC). Results must be confirmed after last documented relapse and after any CD38-directed therapy (if applicable).
• Confirmed availability of cells for a rescue transplant as a therapeutic back-up option as follows:
• Cohort A (AML): Patients must have a suitable stem cell donor available who may donate cells in the event the subject needs to undergo an allogeneic HSCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria; donors must be fully cleared to proceed as the donor.
• Cohort B (MM): Previously harvested autologous stem cells > 2x106/kg CD34+ cells.
  • Adequate organ function defined as:
• Creatinine ≤ 2.5 mg/dl or Creatinine Clearance > 30ml/min b. ALT/AST ≤ 5x upper limit of normal range c. Direct bilirubin ≤ 2.0 mg/dl, unless the subject has Gilbert's syndrome (≤3.0 mg/dl) d. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air e. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
• ECOG Performance Status that is either 0 or 1. 7. Signed informed consent form 8. Subjects of reproductive potential must agree to use acceptable birth control methods.