Spots Global Cancer Trial Database for Genetically Engineered Cells (NY-ESO-1 TCR Engineered T Cells and HSCs) After Melphalan Conditioning Regimen in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Study Description

Brief Summary: This phase I trial studies the best dose and side effects of NY-ESO-1 T cell receptor (TCR) engineered T cells and how well they work with NY-ESO-1 TCR engineered hematopoietic stem cells (HSCs) after melphalan conditioning regimen in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent) or does not respond to treatment (refractory). The melphalan conditioning chemotherapy makes room in the patient's bone marrow for new blood cells and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR T cells and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer. Giving NY-ESO-1 TCR engineered T cells and HSCs after melphalan may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Detailed Description: PRIMARY OBJECTIVES: I. To assess the safety and feasibility of intravenous infusion of autologous peripheral blood mononuclear cells (PBMC) and CD34+ peripheral blood stem cells (PBSC) that have been genetically modified ex vivo to express NY-ESO-1 TCR, following a myeloablative conditioning regimen. Ia. Assessment of toxicities using Common Toxicity Criteria (CTC) and definition of a maximum tolerated dose (MTD). SECONDARY OBJECTIVES: I. TCR engineered hematopoietic stem cell (HSC) engraftment. II. Functional assays for TCR transgenic cells. III. Progression-free survival (PFS) (compare with the duration of the PFS in the last treatment regimen). IV. Durable tumor response in at least 30% of the patients defined as immune-related complete response (irCR) or immune-related partial response (irPR) by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria at 6 months. V. Long-term persistence of TCR transgenic cells (regardless of cell origin) as evidenced by \> 5% of CD3 lymphocytes being NY-ESO-1 specific by major histocompatibility complex (MHC) tetramer assay at 3 and 6 months. VI. Discrimination of TCR transgenic cells resulting from retrovirally-transduced mature lymphocytes and lentivirally-transduced HSCs and their phenotyping. VII. Long term monitoring for replication competent retrovirus and lentivirus. VIII. Analysis of viral insertion sites in long term persisting NY-ESO-1 TCR clones: absence of a clonal expansion of TCR transgenic cells with a particular transgene insertion site (defined as a clone comprising \> 20% of all PBSC-derived gene-marked cells). IX. Gut microbiota pre and post treatment to evaluate the role of microbiota on the therapeutic efficacy of the proposed therapy. OUTLINE: This is a dose-escalation study of autologous NY-ESO-1-specific CD8-positive T lymphocytes. Patients receive melphalan intravenously (IV) over 30 minutes on day -1. Patients then receive autologous NY-ESO-1 CD4-TCR CD34+ HSC IV on day 0 and autologous NY-ESO-1-specific CD8-positive T lymphocytes IV between days 7 and 21. Patients also receive aldesleukin subcutaneously (SC) twice daily (BID) for 14 days on the following day after the T cell infusion (between days 8 and 22). After completion of study treatment, patients are followed up every 6 months for 5 years, then annually for up to 15 years.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: FEMALE

Healthy Volunteers: No

Locations

Contact Details

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