CAR T Cell Therapy for Pediatric Solid Cancers
Trial Summary
What is the purpose of this trial?
This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the safety, feasibility, and efficacy of administering T cell products derived from the research participant's blood that have been genetically modified to express a EGFR-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express EGFR and the selection-suicide marker EGFRt. EGFRt is a protein incorporated into the cell with our EGFR receptor which is used to identify the modified T cells and can be used as a tag that allows for elimination of the modified T cells if needed. On Arm A of the study, research participants will receive EGFR-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at EGFR and CD19, a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T cells will promote the expansion and persistence of the CAR T cells. The CD19 receptor harbors a different selection-suicide marker, HERtG. The primary objectives of the study will be to determine the feasibility of manufacturing the cell products, the safety of the T cell product infusion, to determine the maximum tolerated dose of the CAR T cells products, to describe the full toxicity profile of each product, and determine the persistence of the modified cell in the subject's body on each arm. Subjects will receive a single dose of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to benefit one another once administered to the research participants for improved potential therapeutic effect. The secondary objectives of this protocol are to study the number of modified cells in the patients and the duration they continue to be at detectable levels. The investigators will also quantitate anti-tumor efficacy on each arm. Subjects who experience significant and potentially life-threatening toxicities (other than clinically manageable toxicities related to T cells working, called cytokine release syndrome) will receive infusions of cetuximab (an antibody commercially available that targets EGFRt) or trastuzumab (an antibody commercially available that targets HER2tG) to assess the ability of the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the transferred T cell products.
Will I have to stop taking my current medications?
The trial requires that you stop taking any anti-cancer agents or chemotherapy before enrolling. If you have been on certain therapies, there are specific waiting periods before you can join the trial, such as 7 days after the last chemotherapy or biologic therapy, and 30 days after the last dose of anti-tumor antibody therapy.
What data supports the effectiveness of the treatment EGFR806 CAR T Cell Immunotherapy for pediatric solid cancers?
Research shows that EGFR806 CAR T cells can effectively target and destroy tumor cells expressing a specific form of the EGFR protein, as demonstrated in glioblastoma and non-small cell lung cancer studies. These cells have shown the ability to selectively attack cancer cells without harming normal cells, indicating potential effectiveness in treating solid tumors.12345
Is CAR T Cell Therapy safe for treating pediatric solid cancers?
Research on EGFR-targeted CAR T cell therapy, which is similar to the therapy being studied, shows that it was well-tolerated without severe toxicity in patients with lung cancer. This suggests that the therapy may be generally safe in humans, although serious adverse events have been noted in other CAR T cell therapies, so monitoring is important.12678
How is EGFR806 CAR T Cell Immunotherapy different from other treatments for pediatric solid cancers?
EGFR806 CAR T Cell Immunotherapy is unique because it uses specially engineered T cells to target a specific part of the EGFR protein found on tumor cells, which helps it selectively attack cancer cells without harming normal cells. This approach is different from traditional treatments like chemotherapy and radiation, which can affect both healthy and cancerous cells.1291011
Research Team
Katie Albert, MD
Principal Investigator
Seattle Children's Hospital
Eligibility Criteria
This trial is for children and young adults aged 1-30 with certain non-CNS solid tumors that are recurrent or resistant to treatment. Participants must have a life expectancy of at least 8 weeks, be able to undergo apheresis (a procedure to collect immune cells), and not have had recent myeloablative therapy unless they've recovered. They should not be receiving other cancer treatments or have active infections, CNS pathology, GVHD, primary immunodeficiency, or be pregnant.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive a single dose of genetically modified T cells (CD4 and CD8) targeting EGFR and potentially CD19
Follow-up
Participants are monitored for safety, efficacy, and persistence of CAR T cells in the blood and bone marrow
Long-term follow-up
Participants are monitored for long-term safety and efficacy, including anti-tumor responses and survival characteristics
Treatment Details
Interventions
- EGFR806 CAR T Cell Immunotherapy
EGFR806 CAR T Cell Immunotherapy is already approved in United States for the following indications:
- Recurrent/Refractory Solid Tumors in Children and Young Adults
Find a Clinic Near You
Who Is Running the Clinical Trial?
Seattle Children's Hospital
Lead Sponsor