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.
OUTLINE: This is a dose-escalation study of FH-FOLR1 CAR T. Patients undergo apheresis to obtain T cells for product manufacturing, receive lymphodepleting chemotherapy with fludarabine intravenously (IV) on days -4 to -1, cyclophosphamide IV on days -4 and -3 and receive FH-FOLR1 CAR T IV on day 0. Patients undergo echocardiography (ECHO) at screening, undergo collection of cerebrospinal fluid (CSF), blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo imaging (such as positron emission tomography (PET) scan). After completion of study treatment, patients are followed up for 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Given IV
Undergo CSF and blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Given IV
Undergo ECHO
Given IV
Undergo apheresis
Undergo PET
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium
Seattle, Washington, United States
RECRUITINGIncidence 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.
Time frame: Up to 15 years
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.
Time frame: Up to 28 days
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.
Time frame: At 42 days
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.
Time frame: Up to 15 years
Overall survival
Time frame: From infusion of FH-FOLR1 CAR T cell product to death from any cause, assessed up to 15 years
Disease free survival
Time frame: From T cell infusion to the first observation of disease or death fromany cause, whichever occurs first, assessed up to 15 years
Duration of overall response
Time frame: From the time criteria are met for complete response or partial response until the first date that treatment failure is objectively documented, assessed up to 15 years
Non-relapse mortality
Time frame: From T cell infusion to death where cause of death is not attributable tounderlying disease, assessed up to 15 years
Event free survival
Time frame: From infusion of FH-FOLR1 CAR T product to an event, with eventsdefined as relapse, secondary malignancy, death from any cause, assessed up to 15 years
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