FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia
- Conditions
- Interventions
- Registration Number
- NCT06609928
- Lead Sponsor
- Fred Hutchinson Cancer Center
- Brief Summary
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 ...
- Detailed Description
OUTLINE: This is a dose-escalation study of FH-FOLR1 CAR T.
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Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 12
- 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:
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For subjects who have previously received an allogeneic hematopoietic cell transplantation (HCT), any evidence of AML re-emergence post HCT detectable by flow cytometry.
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First relapse of AML ≤ 6 months from initial diagnosis.
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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).
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Second or greater relapse of AML.
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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:
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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.
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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).
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Tyrosine kinase inhibitor (TKI) use: All TKIs must be discontinued ≥ 3 days prior to enrollment.
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Hydroxyurea: must be discontinued ≥ 1 day prior to enrollment.
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FOLR1 targeting therapy must be discontinued within 30 days prior to enrollment.
- Gene modified cellular therapy:
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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
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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:
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Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female.
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Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female.
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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:
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HIV antigen & antibody.
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Hepatitis B surface antigen.
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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.
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Active malignancy other than acute myeloid leukemia.
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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).
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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.
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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.
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If history of allogeneic stem cell transplant and patient has received donor lymphocyte infusion (DLI) the subject is < 8 weeks from DLI infusion.
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Presence of active severe infection, defined as:
- Positive blood culture within 48 hours of enrollment, OR
- Fever above 38.2 degrees Celsius (C), AND clinical signs of infection within 48 hours of enrollment.
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Primary immunodeficiency syndrome.
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Subject has received prior virotherapy.
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Subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow-up period, required if FH-FOLR1 CAR T cell therapy is administered.
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Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.
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Considered by the investigator to be unable to tolerate a lymphodepleting regimen.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (FH-FOLR1 CAR T) FOLR1 CAR T-cells Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Biospecimen Collection Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Bone Marrow Aspiration Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Bone Marrow Biopsy Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Echocardiography Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Pheresis Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Positron Emission Tomography Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Cyclophosphamide Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up. Treatment (FH-FOLR1 CAR T) Fludarabine Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up.
- Primary Outcome Measures
Name Time Method Incidence of adverse events Up to 15 years 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 Up to 28 days Feasibility will be determined by the rate of manufacturing a FH-FOLR1 CAR T cell product from apheresis product.
- Secondary Outcome Measures
Name Time Method Aplasia At 42 days 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 Up to 15 years 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 From infusion of FH-FOLR1 CAR T cell product to death from any cause, assessed up to 15 years Disease free survival 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 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 From T cell infusion to death where cause of death is not attributable tounderlying disease, assessed up to 15 years Event free survival 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
Trial Locations
- Locations (1)
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium
🇺🇸Seattle, Washington, United States