Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Amino Acids

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunomodulating Agents

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Serine

Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses.

Fludarabine Phosphate

Laboratory Biomarker Analysis

Therapeutic Tumor Infiltrating Lymphocytes

Sylvia M. Lee

This phase II trial studies how well tumor-infiltrating lymphocytes (TIL) after combination chemotherapy works in treating patients with melanoma that has spread to other places in the body. Biological therapies, such as TIL, may stimulate the immune system in different ways and stop tumor cells from growing. 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 TIL after combination chemotherapy may kill more tumor cells.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses.

After completion of study treatment, patients are followed up at 6, 12, and 24 weeks.

Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

Cellular Adoptive Immunotherapy Using Autologous Tumor-Infiltrating Lymphocytes Following Lymphodepletion With Cyclophosphamide and Fludarabine for Patients With Metastatic Melanoma

Assessed using Response Evaluation Criteria in Solid Tumors 1.1 definitions for complete response, partial response, stable disease, and progressive disease. Clinical response will be determined at 6 weeks, 12 weeks and 24 weeks based on RECIST version 1.137 definitions for Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD). Response reported is best response per participant. A complete response will be defined as total regression of all tumors, a PR as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and PD as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter (RECIST v1.1 criteria).

Whole exome and RNA sequencing of tumor cells and normal tissue was performed to identify non synonymous missense mutations, which was then used to generate peptide pools to identify neoantigen-reactive T cells. T-Cell Receptor (TCR) sequencing of T cell clonotypes in blood at time of treatment, 10 months and 24 months was performed and used to assess the persistence of a tumor antigen specific clonotype infused in the TIL product.

Several biomarkers, CXCL13+ CD4 cells, CXCL13+ CD8+ cells, and regulatory cells were evaluated to assess correlation with clinical responses to TIL therapy.

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Associate Professor, Program in Immunology

All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.

Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses.

Aldesleukin: Given IV

Cyclophosphamide: Given IV

Fludarabine Phosphate: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion

Treatment (TIL, Combination Chemotherapy, Aldesleukin)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Sylvia Lee

Number of Participants in Each Clinical Response Category

At time of treatment

10 months post infusion

24 months post infusion

Due to the technical challenges and costs of examining persistence of unmodified TIL cells that do not have a unique tag, the persistence has not been performed in the other patients.

Number of Participants Who Experienced in Vivo Persistence of Adoptively Transferred T Cells Following TIL Infusion

Count of Participants Who Experienced Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

CXCL13+ as % of CD4 T Cell (40% Threshold)

Treg as % of CD4 T Cell (40% Threshold)

CXCL13+ as % of CD8 T Cell (40% Threshold)

Samples from 6 patients were evaluated in depth. Biomarker studies were not performed in all patients due to funding constraints.

A Count of Participants With Biomarker Expression Above Threshold

Treatment (Tumor Infiltrating Lymphocytes (TIL), Combination Chemotherapy, Aldesleukin)

Overall Study

Spots Global Cancer Trial Database for Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial