NCT02500576

Pembrolizumab, Standard Chemotherapy, Tumor Infiltrating Lymphocytes, and High- or Low-Dose Aldesleukin in Treating Patients With Metastatic Melanoma

Phase II Study of MK-3475 in Conjunction With Lymphodepletion, TIL, and High or Low Dose IL-2 in Patients With Metastatic Melanoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase II trial studies how well giving pembrolizumab with standard chemotherapy, tumor infiltrating lymphocytes (TIL), and aldesleukin works in treating patients with melanoma that has spread to other areas of the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, 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. Giving an infusion of TIL, or white blood cells, may help stimulate the immune system to help kill more cells. Aldesleukin may also stimulate the white blood cells to kill melanoma cells. Giving pembrolizumab together with standard chemotherapy, TIL, and high- or low-dose aldesleukin may help stop the melanoma from spreading.

Detailed description

PRIMARY OBJECTIVES: I. Evaluate the overall response rates of pembrolizumab (MK-3475) combined with lymphodepletion, TIL and high or low dose aldesleukin (interleukin-2) therapy in patients with metastatic melanoma. SECONDARY OBJECTIVES: I. Comparison of progression free survival between the treatment arms. II. Comparison of overall survival between the treatment arms. III. Comparison of deep tumor responses (defined as over 60% reduction in tumor burden) between the treatment arms as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. IV. Number of complete responses in both treatment arms. V. Safety evaluations by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4. EXPLORATORY OBJECTIVES: I. Identification of biomarkers predictive of treatment response or failure through immunohistochemistry, flow cytometry, gene expression changes as assessed by NanoString codeset, neo-antigen identification and complementary determining region (CDR)3 sequencing from blood and tumor samples acquired from baseline and on-treatment samples. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard lymphodepleting chemotherapy comprising of cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6 followed by fludarabine phosphate IV piggyback (IVPB) over 15-30 minutes on days -5 to -1. Patients also receive therapeutic tumor infiltrating lymphocytes IV over 15-60 minutes on day 0 followed by high-dose aldesleukin IV over 15 minutes every 8-16 hours for up to 15 doses on days 1-5. Beginning between 21-28 days after TIL infusion, patients receive maintenance therapy comprising of pembrolizumab IV over 30 minutes every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive standard lymphodepleting chemotherapy comprising of cyclophosphamide, fludarabine phosphate, and therapeutic tumor infiltrating lymphocytes as in Arm I, followed approximately 6 hours later by low-dose aldesleukin subcutaneously (SC) once per day (QD) for 14 days. Patients also receive pembrolizumab as in Arm I. After completion of study treatment, patients are followed up every 3 months.

Conditions

• Metastatic Melanoma
• Stage IIIB Cutaneous Melanoma AJCC v7
• Stage IIIC Cutaneous Melanoma AJCC v7
• Stage IV Cutaneous Melanoma AJCC v6 and v7

Interventions

Type	Name	Description
BIOLOGICAL	Aldesleukin	Given IV or SC
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine Phosphate	Given IVPB
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Pembrolizumab	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
BIOLOGICAL	Therapeutic Tumor Infiltrating Lymphocytes	Given IV

Timeline

• Start date: 2015-08-07
• Primary completion: 2022-10-12
• Completion: 2022-10-12
• First posted: 2015-07-16
• Last updated: 2025-01-15
• Results posted: 2025-01-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study