This phase I trial tests the safety, side effects, and best dose of FH-FOLR1 chimeric antigen receptor (CAR) T cells in treating pediatric patients with FOLR1+ acute myeloid leukemia (AML) that has come back after a period of improvement (recurrent) or has not responded to previous treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a FOLR1 on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Chemotherapy drugs, such as fludarabine and cyclophosphamide, are given to a patient before the manufactured FH-FOLR1 CAR T cells are infused back into the patient to assist in the CAR T cell activity in the patient. The trial is evaluating if giving FH-FOLR1 CAR T cell therapy is safe and tolerable for pediatric patients with recurrent or refractory AML.
Subject age ≤ 6 years.
Weight ≥ 7 kilograms.
AML that expresses FOLR1 by flow cytometry as assessed by Hematologics, Inc.
For subjects who have previously received an allogeneic hematopoietic cell transplantation (HCT), any evidence of AML re-emergence post HCT detectable by flow cytometry.
Active malignancy other than acute myeloid leukemia.
History of symptomatic non-AML central nervous system (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).
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.
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.
Single group
FOLR1 CAR T-cells
Biological/VaccineGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo CSF and blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Cyclophosphamide
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Fludarabine
DrugGiven IV
Pheresis
Procedure/SurgeryUndergo apheresis
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Incidence of adverse events
Will be summarized in terms of type, severity, date of onset, and attribution using the Common Terminology for Adverse Events version 5.
Rate of manufacturing anti-FOLR1 chimeric antigen receptor (CAR) T-cells (FH-FOLR1 CAR T) product
Feasibility will be determined by the rate of manufacturing a FH-FOLR1 CAR T cell product from apheresis product.
Aplasia
Will be defined as if a patient has a hypoplastic bone marrow and has failure to recover a peripheral absolute neutrophil count \> 200/uL and a non-transfusion dependent platelet count \> 20,000/uL not due to malignant infiltration or severe infection (defined as ≥ grade 3 infection). Will be assessed using peripheral blood and bone marrow.
Persistence of FH-FOLR1 CAR T
FOLR1 persistence will be defined as detection of the FH-FOLR1 CAR T by flow or polymerase chain reaction above the lower limit of detection. Will be assessed by peripheral blood.
Overall survival
Disease free survival
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Fred Hutchinson Cancer Center
Lead sponsor
Kuni Foundation
Collaborator
