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

NCT06609928 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1124385NCI-2024-06808STUDY00004888
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Recurrent Childhood Acute Myeloid Leukemia; Refractory Childhood Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 28 days

Secondary Outcomes (7)

• Aplasia

  At 42 days

• Persistence of FH-FOLR1 CAR T

  Up to 15 years

• 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

Study Arms (1)

Treatment (FH-FOLR1 CAR T)

EXPERIMENTAL

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.

Biological: FOLR1 CAR T-cells; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Drug: Fludarabine; Procedure: Pheresis; Procedure: Positron Emission Tomography

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (FH-FOLR1 CAR T)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (FH-FOLR1 CAR T)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (FH-FOLR1 CAR T)

Pheresis PROCEDURE

Undergo apheresis

Also known as: Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis, Hemapheresis

Treatment (FH-FOLR1 CAR T)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (FH-FOLR1 CAR T)

FOLR1 CAR T-cells BIOLOGICAL

Given IV

Also known as: Anti-FOLR1 CAR-T Cells, FH-FOLR1 CAR T Cells

Treatment (FH-FOLR1 CAR T)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (FH-FOLR1 CAR T)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (FH-FOLR1 CAR T)

Biospecimen Collection PROCEDURE

Undergo CSF and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (FH-FOLR1 CAR T)

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• If history of allogeneic stem cell transplant and patient has received donor lymphocyte infusion (DLI) the subject is \< 8 weeks from DLI infusion.
• 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.
• Primary immunodeficiency syndrome.
• 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 FH-FOLR1 CAR T cell therapy is administered.
• Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.
• Considered by the investigator to be unable to tolerate a lymphodepleting regimen.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Kuni Foundation: collaborator

Study Sites (1)

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Biopsy; Cyclophosphamide; fludarabine; Blood Component Removal; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Katherine G. Tarlock, MD

  Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine G. Tarlock, MD

CONTACT

206-667-7121; katherine.tarlock@seattlechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: September 24, 2024
• Study Start: February 24, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2042
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)