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

Gary Doolittle

Status and phase

Completed

Phase 1

Conditions

Melanoma

Treatments

Biological: tvs-CTL Vaccine

Study type

Interventional

Funder types

Other

Identifiers

NCT02482532

Mel-2012-01-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

7 patients

Sex

All

Ages

18 to 66 years old

Volunteers

No Healthy Volunteers

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)