HER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma

Part of paid clinical trials in Houston, Texas.

Sponsor
Baylor College of Medicine
Study ID
NCT04995003
Phase
PHASE1
Status
Recruiting
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Conditions

  • Ewing Sarcoma
  • HER-2 Protein Overexpression
  • Osteosarcoma
  • Rhabdomyosarcoma
  • Sarcoma
  • Soft Tissue Sarcoma
  • Synovial Sarcoma
  • Undifferentiated Sarcoma

Eligibility Criteria

Sex
ALL
Age
1 Year - 25 Years
Healthy Volunteers
Not accepted

Interventions

  • T cells or CAR T cells — GENETIC
    There are 2 dose levels: Dose Level 1 (1x10\^8 cells/m2) and Dose Level -1 (5x10\^7 cells/m2). In the event that Dose Level 1 is not tolerable, de-escalation to Dose Level -1 will occur.
  • Pembrolizumab Injectable Product — DRUG
    2 mg/kg/dose (max 200 mg/dose) every 3 weeks
  • Nivolumab Injectable Product — DRUG
    3 mg/kg/dose (\<40kg) or 124 mg (≥40 kg) every 2 weeks

Study Details

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.

Key Dates

Start date
Dec 7, 2021
Status verified
Jan 2026
Primary completion
Jun 30, 2028
Completion
Jun 30, 2043

Study Design

Enrollment
25 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A
    autologous HER2 CAR T cells infused in combination with lymphodepletion chemotherapy and the PD-1 antibody pembrolizumab
  • Experimental: Arm 2
    autologous HER2 CAR T cells infused in combination with lymphodepletion chemotherapy and the PD-1 antibody nivolumab

Primary Outcome Measure

ARM A: Dose-limiting toxicity (DLT) rate by CTCAE v5.0. Neurotoxicity and cytokine release syndrome (CRS) will be graded according to ASTCT Consensus Grading System. [ Time Frame: By day 42 or 14 days after second dose of Pembrolizumab (whichever is longer) ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Texas Children's HospitalHoustonTexas77030-

Find similar trials in Houston, TX

By research site
Texas Children's Hospital· Houston, TX

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