FGFR4 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory Rhabdomyosarcoma

NCT06865664 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001570001570-C
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Rhabdomyosarcoma (RMS) is a cancer of soft tissues. It is the most common soft tissue sarcoma seen in children. RMS cancer cells have a protein called FGFR4 on their surface. Researchers want to try a new kind of treatment for RMS: They will collect a person s own T cells, a type of immune cell; then they will change the T cells so they are better able to target the FGFR4 protein and attack RMS tumor cells. The modified T cells are chimeric antigen receptor (CAR) T cells. The treatment in this study is called FGFR4-CAR T cells. Objective: To test FGFR4-CAR T cells in children and young adults with RMS. Eligibility: People aged 3 to 39 years with RMS. The RMS must have failed to respond or returned after at least 2 rounds of standard treatment. Design: Participants will be screened. They will have physical exam, imaging scans, blood tests, and tests of their heart. They may have a tissue sample taken from their tumor. They will undergo apheresis: Blood will be taken from the body through a catheter. The blood will pass through a machine that separates out the T cells, and the remaining blood will be returned to the body. The collected T cells will be taken to a lab to create FGFR4-CAR T cells. Once the FGFR4-CART cells are ready, participants can receive these T cells. For 4 days they will receive drugs to prepare their body for the FGFR4-CAR T cells. After this, the modified T cells will be infused into a vein. Participants will be then monitored closely to watch for any side effects from the CART cells and be followed to see what effect the CART cells have on their tumors. They will have follow-up visits for up to 5 years. Long-term follow-up will be another 10 years.

Conditions

Rhabdomyosarcoma

Keywords

Sarcoma; Solid Tumor; CAR T Cells; Rhabdomyosarcoma; FGFR4

Outcome Measures

Primary Outcomes (1)

• Estimate the MTD of FGFR4-CAR T cells in children and young adults with recurrent or refractory rhabdomyosarcoma following a cyclophosphamide/fludarabine lymphodepletion regimen

  Estimation of MTD using evaluation of adverse events considered to be a DLT within DLT period as explained in sections Dose Limiting Toxicity (DLT) and Dose Escalation (Arm 1)

  28 days

Secondary Outcomes (4)

• Evaluate the feasibility of manufacturing FGFR4-CAR T cells for children and young adults with recurrent or refractory rhabdomyosarcoma

  Initiation of manufacturing FGFR4-CAR T cells of the first participant until completion of CART cell manufacturing of the last participant.

• Evaluate the safety of FGFR4-CAR T cells therapy in children and young adults with recurrent or refractory rhabdomyosarcoma

  6 months

• Evaluate progression-free survival

  Baseline, Day 30, 3, 6, 9, 12 months after cell infusion, every 3 months after that for year 2, every 12 months for years 3-5.

• Evaluate ORR for those with measurable disease defined as CR + PR according to RECIST 1.1 in children and young adults with rhabdomyosarcoma

  Baseline, Day 30, 3, 6, 9, 12 months after cell infusion, every 3 months after that for year 2, every 12 months for years 3-5.

Study Arms (2)

Arm 1

EXPERIMENTAL

Lymphodepleting preparative regimen (fludarabine and cyclophosphamide) followed by infusion of FGFR4-CAR T cells escalation/de-escalation dose levels

Drug: fludarabine; Drug: cyclophosphamide; Drug: cetuximab; Biological: FGFR4-CAR T Cells

Arm 2

EXPERIMENTAL

Lymphodepleting preparative regimen (fludarabine and cyclophosphamide) followed by infusion of FGFR4-CAR T cells at the MTD

Drug: fludarabine; Drug: cyclophosphamide; Drug: cetuximab; Biological: FGFR4-CAR T Cells

Interventions

FGFR4-CAR T Cells BIOLOGICAL

Single intravenous (IV) infusion on Day 0

Arm 1; Arm 2

fludarabine DRUG

30 mg/m2 per day IV on days -5, -4, -3, -2

Arm 1; Arm 2

cyclophosphamide DRUG

500 mg/m2 per day IV on days -4, -3, -2

Arm 1; Arm 2

cetuximab DRUG

Participants Age \>=18 years, based on FDA approved dosing: Loading dose of 400 mg/m2 IV, followed by 250 mg/m2 IV weekly for a total of 4 doses. Participants Age \<18 years, based on phase I data of cetuximab in children: Dose of 250 mg/m2 IV administered over 1 hour weekly for a total of 4 doses.

Arm 1; Arm 2

Eligibility Criteria

• Age: 3 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed rhabdomyosarcoma by the NCI Department of Pathology.
• Note: Since FGFR4 expression is universal in rhabdomyosarcoma, confirmation of FGFR4 expression is not required.
• Relapsed or refractory rhabdomyosarcoma after at least two (2) cancer treatment regimens i.e., participants should have relapsed or progressed after upfront therapy (that includes any systemic chemotherapy with or without local control) as well as at least one salvage therapy (which can be systemic therapy, radiation, or surgery).
• No available alternative curative therapies per standard of care.
• Participants must have measurable disease per RECIST 1.1 or non-measurable disease on imaging.
• Age \>= 3 and \<= 39 years old.
• Weight \>=15 kg.
• Performance status: Karnofsky \>= 50% (\>= 16 years) or Lansky \>= 50% (\< 16 years).
• Note: Participants who are unable to walk because of paralysis, but who are upright in a wheelchair will be considered ambulatory for calculating the performance score.
• Participants must be willing to accept blood transfusions.
• Adequate organ and marrow function as defined below:
• Organ: Bone Marrow Function\*
• Laboratory Element: Absolute neutrophil count; Minimum Requirement \>= 500/mcL
• Laboratory Element: Platelets; Minimum Requirement \>= 50,000/mcL
• \*Transfusion independent (defined as no transfusion in the prior 7 days) for participants without bone marrow involvement. Participants who have bone marrow involvement with tumor are exempt from the platelet requirement and will not be evaluable for hematological toxicities. Participants must not be refractory to transfusions.

You may not qualify if:

• Prior therapy with the following prior to apheresis:
• tyrosine kinase inhibitor, targeted agent, or metronomic non-myelosuppressive regimen within \<= 1 week
• systemic chemotherapy within \<= 2 weeks
• antineoplastic antibody therapy, checkpoint inhibitors, or vaccine therapy, within \<= 3 weeks or 5 half-lives (whichever is shorter)
• radiation within \<= 3 weeks (\<= 6 weeks if CNS or lung fields have been radiated or in case of craniospinal irradiation of radiation of \>=50% of bony pelvis and \<=12 weeks in case of total body irradiation). Note: There is no time restriction if the volume of bone marrow treated is less than 10% and the participant has measurable/evaluable disease outside the radiation port
• any investigational agents within \<= 4 weeks
• autologous stem cell infusion following myeloablative therapy within \<= 6 weeks
• genetically modified T cell, NK cell, or dendritic cell therapy within \<= 6 weeks
• allogeneic stem cell transplant/infusion within \<=12 weeks or evidence of active graft versus host disease (GVHD)
• Participants receiving more than physiologic dosing of systemic steroids (3 mg/m\^2/day of prednisone equivalent).
• History of severe, immediate hypersensitivity reaction attributed to any agents used in the study or in the manufacturing of the cells.
• Second malignancy at any time.
• Primary immunodeficiency.
• Seropositive for human immunodeficiency virus (HIV) antibody.
• Seropositive for hepatitis C (HCV) or positive for Hepatitis B (HBV) surface antigen (HbsAg).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Rhabdomyosarcoma; Sarcoma

Interventions

fludarabine; Cyclophosphamide; Cetuximab

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Srivandana Akshintala, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI POB Solid Tumor Referral Team

CONTACT

(240) 858-7012; ncipobstreferrals@mail.nih.gov

Srivandana Akshintala, M.D.

CONTACT

(240) 858-3448; srivandana.akshintala@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2025
• First Posted: March 10, 2025
• Study Start: September 22, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2029
• Last Updated: March 16, 2026

Record last verified: 2026-03-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)