CAR T-Cell Therapy + Checkpoint Inhibitors for Sarcoma
Trial Summary
What is the purpose of this trial?
The purpose of this study is to learn whether it is safe to give HER2-CAR T cells in combination with an immune checkpoint inhibitor drug (pembrolizumab or nivolumab), to learn what the side effects are, and to see whether this therapy might help patients with sarcoma. Another goal of this study is to study the bacteria found in the stool of patients with sarcoma who are being treated with HER2 CAR T cells and immune checkpoint inhibitor drugs to see if the types of bacteria influence how well the treatment works. The investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to see if they can put a new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new gene that the investigators will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor Receptor 2) that binds to sarcoma cells. In addition, it contains CD28, which stimulated T cells and make them last longer. After this new gene is put into the T cell, the T cell becomes known as a chimeric antigen receptor T cell or CAR T cell. In another clinical study using these CAR T cells targeting HER2 as well as other studies using CAR T cells, investigators found that giving chemotherapy before the T cell infusion can improve the effect the T cells can have. Giving chemotherapy before a T cell infusion is called lymphodepletion since the chemotherapy is specifically chosen to decrease the number of lymphocytes in the body. Decreasing the number of the patient's lymphocytes first should allow the infused T cells to expand in the body, and potentially kill cancer cells more effectively. The chemotherapy used for lymphodepletion is a combination of cyclophosphamide and fludarabine. After the patient receives the lymphodepletion chemotherapy and CAR T cells during treatment on the study, they will receive an antibody drug called an immune checkpoint inhibitor, pembrolizumab or nivolumab. Immune checkpoint inhibitors are drugs that remove the brakes on the immune system to allow it to act against cancer.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you must be at least 4 weeks from your last cytotoxic chemotherapy and at least 7 days or 3 drug half-lives from your last targeted therapy, and you must have recovered from any acute toxic effects.
What data supports the effectiveness of the treatment CAR T-Cell Therapy + Checkpoint Inhibitors for Sarcoma?
Research shows that fludarabine and cyclophosphamide, when used together, can effectively reduce tumor cells and create a favorable environment for T cell activation, which is crucial for CAR T-cell therapy. Additionally, fludarabine has been shown to improve outcomes in CAR T-cell therapy for leukemia, suggesting potential benefits in similar treatments.12345
Is CAR T-Cell Therapy with Cyclophosphamide and Fludarabine safe for humans?
Cyclophosphamide and fludarabine, used before CAR T-cell therapy, can cause significant reduction in certain immune cells, but they also create a suitable environment for T-cell activation. Some patients may experience side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), but these risks can be managed with careful dosing.15678
How is the CAR T-Cell Therapy + Checkpoint Inhibitors treatment for sarcoma different from other treatments?
This treatment is unique because it uses genetically engineered T cells (a type of immune cell) to specifically target and kill cancer cells by recognizing a protein called HER2 on their surface, which is different from traditional chemotherapy that attacks all rapidly dividing cells. Additionally, the combination with checkpoint inhibitors helps to enhance the immune response against the tumor, offering a novel approach for sarcomas where standard treatments are limited.19101112
Research Team
Meenakshi Hegde, MD
Principal Investigator
Baylor College of Medicine
Shoba Navai, MD
Principal Investigator
Baylor College of Medicine
Nabil Ahmed, MD
Principal Investigator
Baylor College of Medicine
Eligibility Criteria
This trial is for young patients aged 1-25 with HER2-positive sarcoma, who have normal heart function and organ health. They must not be pregnant or breastfeeding, agree to use contraception if of childbearing potential, and have no severe allergies to the drugs used in this study. Patients with certain heart conditions, active infections, HIV or tuberculosis are excluded.Inclusion Criteria
Exclusion Criteria
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Lymphodepletion Chemotherapy
Participants receive cyclophosphamide for 2 days followed by fludarabine for 5 days to prepare for CAR T cell infusion
CAR T Cell Infusion
Participants receive HER2 CAR T cells intravenously, followed by monitoring for up to 4 hours
Checkpoint Inhibitor Treatment
Participants receive pembrolizumab every three weeks or nivolumab every two weeks, starting one week after CAR T cell infusion
Follow-up
Participants are monitored for safety and effectiveness after treatment, including blood tests and imaging studies
Treatment Details
Interventions
- Cyclophosphamide and Fludarabine (Alkylating agents)
- HER2-CAR T cells (CAR T-cell Therapy)
- Nivolumab (Checkpoint Inhibitor)
- Pembrolizumab (Checkpoint Inhibitor)
Find a Clinic Near You
Who Is Running the Clinical Trial?
Baylor College of Medicine
Lead Sponsor
National Institutes of Health (NIH)
Collaborator
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator
The Faris Foundation USA
Collaborator
Stand Up To Cancer
Collaborator
Triumph Over Kid Cancer Foundation
Collaborator
St. Baldrick's Foundation
Collaborator
National Cancer Institute (NCI)
Collaborator