Vaccine Enriched, Autologous, Activated T-Cells Directed to Tumor in Patients With Relapsed/Refractory Melanoma

NCT ID: NCT02482532

Last Updated: 2022-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-06
• Study Completion Date: 2021-09-13

Brief Summary

The researchers will investigate if modified T-cells from a patients own system can be utilized to find and destroy metastatic melanoma tumor and thus improve patient outcomes.

Detailed Description

The rate of progression free survival at one (1) year is < 20% for patients with stage IV metastatic melanoma, despite aggressive cytotoxic chemotherapy regimens and newly approved immunomodulatory and targeted therapy. Immunotherapy seems to hold the most promise for achieving prolonged survival or even cure, therefore,efforts have focused on several different approaches. Such approaches have used tumor vaccination, adoptive transfer of tumor infiltrating lymphocytes, and even monoclonal antibodies, unconjugated or conjugated to cytokines, toxins, or radionucleotides.

The tumor-associated antigen GD2 has been noted on the surface of several tumors, most notably neuroblastoma, but is expressed on melanoma as well. Clinical studies have shown activity of a GD2-specific chimeric T-cell receptor expressed on activated, autologous, T-cells in patients with neuroblastoma. It is the investigators intention to enrich peripheral blood mononuclear cells (PBMC) of patients with stage IV metastatic melanoma with vaccine-specific T-cells through pre-harvest/ phlebotomy vaccination with common, well understood vaccines. The investigators will then modify the T-cells to attack the GD2 antigen. These tumor redirected, vaccine specific, activated T-cells will then be infused into the patient following revaccination with the common vaccines. The Investigators will monitor expansion of the modified T-cells through serial polymerase chain reaction (PCR) assays following vaccination.

The Investigators then intend to re-vaccinate with the selected vaccines one month following infusion and monitor for expansion of the modified T-cells.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

tvs-CTL Vaccine

Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.

Group Type: EXPERIMENTAL

tvs-CTL Vaccine

Intervention Type: BIOLOGICAL

autologous, 14g2a.zeta chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)

Interventions

tvs-CTL Vaccine

autologous, 14g2a.zeta chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Metastatic, surgically unresectable melanoma or newly diagnosed melanoma of any stage, where the patient is unable to receive or complete standard therapy
• Life expectancy of at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
• Laboratory Values

• absolute neutrophil count > 500 microliters (mcL)
• platelet > 50,000 mcL
• serum aspartate aminotransferase (AST) < 5 x institutional upper limit of normal (IULN)
• total bilirubin < 3 x IULN
• serum creatinine < 3 x IULN
• Pulse oximetry of > 95% on room air.
• Must have recovered from the toxic effects of all prior chemotherapy

Exclusion Criteria

• Patients with rapidly progressive disease.
• Patient is currently receiving any investigational drugs
• Current cardiomegaly or bilateral pulmonary infiltrates on chest radiograph, pulmonary metastatic lesions are allowed
• Patients must not have tumor in a location where enlargement could cause airway obstruction
• Patient is pregnant or lactating
• History of hypersensitivity reactions to murine protein-containing products.
• Currently receiving immunosuppressive drugs such as corticosteroids (excluding topical treatment), tacrolimus or cyclosporin
• Received any tumor vaccines within previous six weeks
• Known hypersensitivity to rat monoclonal antibodies
• History of severe allergic reaction to Hepatitis B vaccine, Polio vaccine or Tetanus, Diphtheria, Pertussis vaccine (DTP, Tdap, DT or Td).
• Allergy to baker's yeast or other components of the vaccines.
• History of allergy to the antibiotics Neomycin, Streptomycin or Polymyxin B
• History of coma, long/multiple seizures within 7 days after DTP or Tdap, unless a cause other than the vaccine was indicated.
• Melanoma involvement of the central nervous system
• Chemotherapy given within the last 28 days
• Presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 66 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gary Doolittle

OTHER

Sponsor Role: lead

Responsible Party

Gary Doolittle

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gary Doolittle, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

KU Cancer Center

Fairway, Kansas, United States

Countries

United States

Other Identifiers

Mel-2012-01-01

Identifier Type: -

Identifier Source: org_study_id