A Study of CLEC2A CAR T for Pediatric and Adult Patients With Relapsed or Refractory AML

Prior treatment

• Active malignancy other than acute myeloid leukemia.
  • Treated localized breast cancer, breast cancer receiving endocrine therapy alone, non-melanoma skin cancer, localized prostate cancer, prostate cancer receiving endocrine therapy or being managed with observation all will be allowed.
• If history of allogeneic stem cell transplant: active GVHD or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment.
• Subject has received prior virotherapy.
• Subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow-up period, required if SC-CAR.CLEC2Av1 CAR T cell therapy is administered.

Other illness

• History of symptomatic non-AML CNS disease or ongoing symptomatic CNS disease requiring medical intervention, including paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder (subjects with non-febrile seizure disorder controlled on anti-epileptic medication and without seizure activity within 1 month are eligible).
• Presence of active severe infection, defined as:
  • Positive blood culture within 48 hours of enrollment, OR
  • Fever above 38.2° C, AND clinical signs of infection within 48 hours of enrollment.
• Primary immunodeficiency syndrome.
• Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.

Lab values

• If history of allogeneic stem cell transplant and patient has received donor lymphocyte infusion (DLI) the subject is \<8 weeks from DLI infusion.

Other

• CNS AML involvement that is symptomatic and in the opinion of the investigator, cannot be controlled during the interval between enrollment and T cell infusion.
• Considered by the investigator to be unable to tolerate a lymphodepleting regimen.
• Pregnancy or lactation

• Subject age ≤ 70 years
• Weight ≥ 7 kilograms
• AML that expresses CLEC2A by flow cytometry as assessed by Hematologics, Inc. Laboratory and meets one of the below definitions:
  • for subjects who have previously received an allogeneic HCT, any evidence of AML post HCT detectable by flow cytometry.
  • first or greater relapse of AML.
  • refractory AML, defined as ≥ 0.1% leukemic cells determined by flow cytometry or \>1% on biopsy after 2 cycles of chemotherapy.
• Able to tolerate apheresis
• Life expectancy ≥ 8 weeks
• Has an appropriate stem cell donor source identified
• Lansky performance status score of ≥ 50 for subjects \<16 years of age or Karnofsky score ≥ 50 for subjects ≥ 16 years. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status
• The subject must discontinue all anticancer agents and radiotherapy and, in the opinion of the investigator, have fully recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy:
  • Chemotherapy and biologic agents: All chemotherapy and biologic therapy not specifically mentioned below must be discontinued ≥ 14 days prior to enrollment, with the exception of intrathecal chemotherapy for which there is not a required washout period.
  • Steroid use: All corticosteroid therapy (unless physiologic replacement dosing) must be discontinued ≥ 7 days prior to enrollment, unless being used to treat GVHD (if being used to treat GVHD see Section 6.4.2 for requirements).
  • Tyrosine Kinase Inhibitor (TKI) use: All TKIs must be discontinued ≥ 3 days prior to enrollment.
  • Hydroxyurea: must be discontinued ≥ 1 day prior to enrollment.
• Gene Modified cellular therapy:
  • Must be at least 30 days from most recent gene modified cell therapy infusion and document no evidence of modified cells in the peripheral blood OR
  • Must be at least 60 days from most recent gene modified cell therapy.
• Adequate organ function as indicated by:
  • Renal: Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) based on the following: Age: 1 to \< 2 yrs: Male: 0.6 mg/dL. Female: 0.6 mg/dL Age: 2 to \< 6 yrs: Male: 0.8 mg/dL. Female: 0.8 mg/dL Age: 6 to \<10 yrs: Male: 1 mg/dL. Female: 1 mg/dL Age: 10 to \< 13 yrs: Male: 1.2 mg/dL. Female: 1.2 mg/dL Age: 13 to \< 16 yrs: Male: 1.5 mg/dL. Female: 1.4 mg/dL Age: ≥ 16 yrs Male: 1.7 mg/dL. Female: 1.4 mg/dL
• Hepatic: Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL AND ALT (SGPT) ≤ 5 times ULN.
• Cardiac: Shortening fraction ≥ 28% OR ejection fraction (EF) ≥ 50% as measured by echocardiogram.
• Respiratory: Oxygen saturation ≥ 92% on room air without supplemental oxygen or mechanical ventilation.
• Laboratory values meet the following criteria:
  • Absolute Lymphocyte Count (ALC) ≥ 100 cells/uL. b) Virology Testing negative within 3 months prior to enrollment, to include: i. HIV antigen \& antibody. ii. Hepatitis B surface antigen. iii. Hepatitis C antibody OR if positive, Hepatitis C PCR is negative.
• If subject is of childbearing or child-fathering potential, must agree to use highly effective contraception (Appendix 7) from the time of initial consent through 12 months following the infusion of investigational product on this trial.
• Subject and/or legally authorized representative has signed the Informed Consent Form for this study.