Metastatic Melanoma Clinical Trial
Official title:
A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies
This phase I/IIa trial studies the side effects and best dose of gene-modified T cells when given with or without decitabine, and to see how well they work in treating patients with malignancies expressing cancer-testis antigens 1 (NY-ESO-1) gene that have spread to other places in the body (advanced). A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Placing a modified gene for NY-ESO-1 into the patients' T cells in the laboratory and then giving them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving gene-modified T cells with or without decitabine works better in treating patients with malignancies expressing NY-ESO-1.
PRIMARY OBJECTIVE: I. To evaluate the safety and feasibility of adoptive transfer of TGFbDNRII-transduced autologous tumor infiltrating lymphocytes (autologous NY-ESO-1 TCR/dnTGFbetaRII transgenic T cells). SECONDARY OBJECTIVES: I. NY-ESO-1 TCR/ dnTGFbetaRII transgenic T cell persistence by analyzing serial peripheral blood samples for the presence of T cells with the NY-ESO-1 TCR by tetramer analysis. II. To study T cell differentiation that correlates with higher anti-tumor responses. III. To test the hypothesis that NY-ESO-1 TCR/dnTGFbetaRII will constitute in cells more efficient in inducing tumor regression. IV. Determine objective tumor responses by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1. EXPLORATORY OBJECTIVE: I. To evaluate the role of microbiota on the therapeutic efficacy of the proposed therapy. OUTLINE: This is a phase I, dose-escalation study of NY-ESO-1 TCR/TGFbDNRII-transduced TILs followed by a phase IIa study. Participants are assigned 1 to 2 cohorts. COHORT I: Patients undergo leukapheresis on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -5 and -4. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed. COHORT II: Patients undergo leukapheresis on day -6 and receive decitabine IV over 1 hour on days -6 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed. After completion of study treatment, patients are followed up at weeks 1-4, 6, 8, and 12, at 6 and 9 months, every 6 months for 5 years, and then yearly for 10 years. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT02224781 -
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT05470283 -
Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma
|
Phase 1 | |
Recruiting |
NCT05388877 -
E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma
|
Phase 1 | |
Active, not recruiting |
NCT05103891 -
Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations
|
Phase 1 | |
Completed |
NCT00414765 -
Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
|
Phase 4 | |
Completed |
NCT02857270 -
A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer
|
Phase 1 | |
Completed |
NCT01621490 -
PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
|
Phase 1 | |
Recruiting |
NCT05779423 -
Cryoablation+Ipilimumab+Nivolumab in Melanoma
|
Phase 2 | |
Active, not recruiting |
NCT04940299 -
Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
|
Phase 2 | |
Active, not recruiting |
NCT02278887 -
Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT02360579 -
Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT02521870 -
A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
|
Phase 1/Phase 2 | |
Completed |
NCT02177110 -
A Translational Systems Medicine Approach to Provide Predictive Capacity for Therapy Response in Advanced or Metastatic Malignant Melanoma
|
||
Withdrawn |
NCT01340729 -
Open-Label Study of TPI 287 for Patients With Metastatic Melanoma
|
Phase 1/Phase 2 | |
Withdrawn |
NCT01416844 -
Study of Immune Responses in Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT01468818 -
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00984464 -
Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00631618 -
Clinical Trial of Sutent to Treat Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT00571116 -
Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy
|
Phase 1 | |
Recruiting |
NCT00226473 -
Standard Palliative Care Versus Standard Palliative Care Plus Polychemotherapy in Metastasized Malignant Melanoma
|
Phase 4 |