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

NCT ID: NCT06609928

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-24

Study Completion Date

2042-10-01

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Recurrent Childhood Acute Myeloid Leukemia Refractory Childhood Acute Myeloid Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (FH-FOLR1 CAR T)

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.

Group Type EXPERIMENTAL

FOLR1 CAR T-cells

Intervention Type BIOLOGICAL

Given IV

Biospecimen Collection

Intervention Type PROCEDURE

Undergo CSF and blood sample collection

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Cyclophosphamide

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Fludarabine

Intervention Type DRUG

Given IV

Pheresis

Intervention Type PROCEDURE

Undergo apheresis

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Interventions

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FOLR1 CAR T-cells

Given IV

Intervention Type BIOLOGICAL

Biospecimen Collection

Undergo CSF and blood sample collection

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Cyclophosphamide

Given IV

Intervention Type DRUG

Echocardiography Test

Undergo ECHO

Intervention Type PROCEDURE

Fludarabine

Given IV

Intervention Type DRUG

Pheresis

Undergo apheresis

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET

Intervention Type PROCEDURE

Other Intervention Names

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Anti-FOLR1 CAR-T Cells FH-FOLR1 CAR T Cells Biological Sample Collection Biospecimen Collected Specimen Collection Biopsy of Bone Marrow Biopsy, Bone Marrow (-)-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 EC Echocardiography Fluradosa Apheresed Apheresis Blood Component Removal Collection, Apheresis/Leukapheresis Hemapheresis 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

Eligibility Criteria

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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.

Exclusion Criteria

* 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.
Maximum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kuni Foundation

UNKNOWN

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katherine G. Tarlock, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Katherine G. Tarlock, MD

Role: CONTACT

206-667-7121

Facility Contacts

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Katherine G. Tarlock, MD

Role: primary

206-667-7121

Other Identifiers

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NCI-2024-06808

Identifier Type: REGISTRY

Identifier Source: secondary_id

STUDY00004888

Identifier Type: OTHER

Identifier Source: secondary_id

RG1124385

Identifier Type: -

Identifier Source: org_study_id

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