FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1 Study of FOLR1 CAR T for Pediatric Patients With FOLR1/CBFA2T3::GLIS2+ Relapsed or Refractory AML
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- Up to 6 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 15 years
- Procedures mentioned: Infusions, Blood draws, Biopsies
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers."
- "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."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests the safety, side effects, and best dose of FH-FOLR1 CAR T-cell therapy. It is for children age 6 or younger with acute myeloid leukemia (AML), a blood cancer, that has come back or has not responded to treatment and has a marker called FOLR1. The treatment changes the child's immune cells in a lab to help them attack cancer cells.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Age 6 or younger and weigh at least 7 kilograms (about 15 pounds).
- Have AML with the FOLR1 marker confirmed by a lab test.
- Have AML that returned after a donor stem cell transplant, returned within 6 months of diagnosis, or returned at least twice. A later first return must leave at least 0.05% cancer cells after another treatment cycle. AML that did not respond must have at least 0.1% cancer cells by a cell test or more than 1% by biopsy after 2 chemotherapy cycles.
- Be able to have blood cells collected by a machine, have a suitable stem cell donor source, and be expected to live at least 8 weeks.
- Meet the study's daily activity score of at least 50. Children who use a wheelchair because of paralysis may still qualify.
- Stop cancer treatments for the required times and recover from major side effects. Earlier treatment with gene-changed cells must meet special waiting and testing rules.
- Meet kidney, liver, heart, oxygen, and immune cell test limits. Required HIV and hepatitis tests must show no infection under the study's rules.
- The child or their legal representative must sign the study consent form.
Who can't join
- Have another active cancer besides AML.
- Have certain past or current brain or nerve problems with symptoms. A seizure disorder may be allowed if controlled with medicine and no seizures occurred within 1 month.
- Have AML in the brain or spinal cord causing symptoms that the study doctor cannot control before the T-cell treatment.
- After a donor stem cell transplant, have active graft-versus-host disease, where donor cells attack the body, or have used medicines to prevent or treat it within 4 weeks. A donor immune cell infusion less than 8 weeks ago also excludes a child.
- Have a severe active infection: a positive blood culture within 48 hours, or fever above 38.2°C with signs of infection within 48 hours.
- Have a primary immune deficiency, a condition that weakens the body's defenses, or have had virus-based treatment before.
- The child or legal representative will not agree to the required 15-year follow-up if CAR T-cell treatment is given.
- The study doctor believes another condition makes treatment unsuitable, or the child cannot tolerate the chemotherapy used to lower immune cells before treatment.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
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.
Study sites (1)
WA
- Fred Hutch/University of Washington/Seattle Children's Cancer Consortium · Seattle, WA 98109Katherine G. Tarlock, MD · Study contact · 206-667-7121 · katherine.tarlock@seattlechildrens.orgKatherine G. Tarlock, MD · Principal investigatorMore trials in Seattle