RECRUITING

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

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Conditions

Recurrent Childhood Acute Myeloid LeukemiaRefractory Childhood Acute Myeloid Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1 Study of FOLR1 CAR T for Pediatric Patients With Relapsed or Refractory AML

Quick Facts

Study Start:2025-02-24
Study Completion:2042-10-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06609928

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 6 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD
Inclusion CriteriaExclusion Criteria
  1. * Subject age ≤ 6 years.
  2. * Weight ≥ 7 kilograms.
  3. * AML that expresses FOLR1 by flow cytometry as assessed by Hematologics, Inc.
  4. * For subjects who have previously received an allogeneic hematopoietic cell transplantation (HCT), any evidence of AML re-emergence post HCT detectable by flow cytometry.
  5. * First relapse of AML ≤ 6 months from initial diagnosis.
  6. * 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).
  7. * Second or greater relapse of AML.
  8. * Refractory AML, defined as ≥ 0.1% leukemic cells determined by flow cytometry or \> 1% on biopsy after 2 cycles of chemotherapy.
  9. * Able to tolerate apheresis.
  10. * Life expectancy ≥ 8 weeks.
  11. * Has an appropriate stem cell donor source identified.
  12. * 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.
  13. * 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:
  14. * 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.
  15. * 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).
  16. * Tyrosine kinase inhibitor (TKI) use: All TKIs must be discontinued ≥ 3 days prior to enrollment.
  17. * Hydroxyurea: must be discontinued ≥ 1 day prior to enrollment.
  18. * FOLR1 targeting therapy must be discontinued within 30 days prior to enrollment.
  19. * Gene modified cellular therapy:
  20. * 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
  21. * Must be at least 60 days from most recent gene modified cell therapy.
  22. * Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) based on the following:
  23. * Age 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female.
  24. * Age 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female.
  25. * Age 6 to \< 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female.
  26. * Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL.
  27. * Alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 5 times ULN.
  28. * Shortening fraction ≥ 28% OR ejection fraction (EF) ≥ 50% as measured by echocardiogram.
  29. * Oxygen saturation ≥ 92% on room air without supplemental oxygen or mechanical ventilation.
  30. * Absolute lymphocyte count (ALC) ≥ 100 cells/uL.
  31. * Virology testing negative within 3 months prior to enrollment, to include:
  32. * HIV antigen \& antibody.
  33. * Hepatitis B surface antigen.
  34. * Hepatitis C antibody OR if positive, hepatitis C polymerase chain reaction (PCR) is negative.
  35. * Subject and/or legally authorized representative has signed the informed consent form for this study.
  1. * Active malignancy other than acute myeloid leukemia.
  2. * 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).
  3. * 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.
  4. * 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.
  5. * If history of allogeneic stem cell transplant and patient has received donor lymphocyte infusion (DLI) the subject is \< 8 weeks from DLI infusion.
  6. * Presence of active severe infection, defined as:
  7. * Positive blood culture within 48 hours of enrollment, OR
  8. * Fever above 38.2 degrees Celsius (C), AND clinical signs of infection within 48 hours of enrollment.
  9. * Primary immunodeficiency syndrome.
  10. * Subject has received prior virotherapy.
  11. * 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.
  12. * Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.
  13. * Considered by the investigator to be unable to tolerate a lymphodepleting regimen.

Contacts and Locations

Study Contact

Katherine G. Tarlock, MD
CONTACT
206-667-7121
katherine.tarlock@seattlechildrens.org

Principal Investigator

Katherine G. Tarlock, MD
PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium
Seattle, Washington, 98109
United States

Collaborators and Investigators

Sponsor: Fred Hutchinson Cancer Center

  • Katherine G. Tarlock, MD, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-24
Study Completion Date2042-10-01

Study Record Updates

Study Start Date2025-02-24
Study Completion Date2042-10-01

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Childhood Acute Myeloid Leukemia
  • Refractory Childhood Acute Myeloid Leukemia