Trial Title:
FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT ID:
NCT06609928
Condition:
Recurrent Childhood Acute Myeloid Leukemia
Refractory Childhood Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cyclophosphamide
Fludarabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
FOLR1 CAR T-cells
Description:
Given IV
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
Anti-FOLR1 CAR-T Cells
Other name:
FH-FOLR1 CAR T Cells
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo CSF and blood sample collection
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Treatment (FH-FOLR1 CAR T)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Asta B 518
Other name:
B 518
Other name:
B-518
Other name:
B518
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR 138719
Other name:
WR- 138719
Other name:
WR-138719
Other name:
WR138719
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
EC
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Given IV
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
Fluradosa
Intervention type:
Procedure
Intervention name:
Pheresis
Description:
Undergo apheresis
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
Apheresed
Other name:
Apheresis
Other name:
Blood Component Removal
Other name:
Collection, Apheresis/Leukapheresis
Other name:
Hemapheresis
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET
Arm group label:
Treatment (FH-FOLR1 CAR T)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
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.
Detailed description:
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.
Criteria for 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.
Gender:
All
Minimum age:
N/A
Maximum age:
6 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium
Address:
City:
Seattle
Zip:
98109
Country:
United States
Contact:
Last name:
Katherine G. Tarlock, MD
Phone:
206-667-7121
Email:
katherine.tarlock@seattlechildrens.org
Investigator:
Last name:
Katherine G. Tarlock, MD
Email:
Principal Investigator
Start date:
February 1, 2025
Completion date:
October 1, 2042
Lead sponsor:
Agency:
Fred Hutchinson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Kuni Foundation
Agency class:
Other
Source:
Fred Hutchinson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06609928
