FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• •Subject age ≤ 6 years.
• •Weight ≥ 7 kilograms.
• •AML that expresses FOLR1 by flow cytometry as assessed by Hematologics, Inc.
• •Laboratory and meets one of the below definitions:
• •For subjects who have previously received an allogeneic hematopoietic cell transplantation (HCT), any evidence of AML re-emergence post HCT detectable by flow cytometry.
• •First relapse of AML ≤ 6 months from initial diagnosis.
• •First relapse of AML \> 6 months from initial diagnosis with minimal residual disease (MRD) ≥ 0.05% by flow cytometry after at least one re-induction attempt (one cycle of therapy).
• •Second 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. 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 graft-versus-host disease (GVHD) (if being used to treat GVHD see 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.
• •FOLR1 targeting therapy must be discontinued within 30 days 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.
• •* Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) based on the following:
• •Age 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female.
• •Age 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female.
• •Age 6 to \< 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female.
• •* Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL.
• •* Alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 5 times ULN.
• •* Shortening fraction ≥ 28% OR ejection fraction (EF) ≥ 50% as measured by echocardiogram.
• •* Oxygen saturation ≥ 92% on room air without supplemental oxygen or mechanical ventilation.
• •* Absolute lymphocyte count (ALC) ≥ 100 cells/uL.
• •* Virology testing negative within 3 months prior to enrollment, to include:
• •HIV antigen \& antibody.
• •Hepatitis B surface antigen.
• •Hepatitis C antibody OR if positive, hepatitis C polymerase chain reaction (PCR) is negative.
• •* Subject and/or legally authorized representative has signed the informed consent form for this study.