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

Phase I Study of Vaccine Enriched, Autologous, Activated T-Cells Redirected to the Tumor Marker GD2 in Patients With Relapsed/Refractory Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: tvs-CTL Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Fairway, Kansas, United States, 66205
      • KU Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tvs-CTL Vaccine; Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.	Biological: tvs-CTL Vaccine; autologous, 14g2a.zeta chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of infusion related adverse events to evaluate the safety of infused T-cells	To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)	4 weeks
PCR measurement of retroviral construct to measure persistence of infused T-cells	To evaluate how long the infused T-cells remain in the blood stream	4 weeks
Measurement of replication competent retrovirus to evaluate the safety of infused T-cells	To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCR measurement of retroviral construct to measure the expansion of infused T-cells	To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines	12 months
PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination	To compare the frequency of tvs-CTL in the peripheral blood, after revaccination, to the frequency noted in the prior study of autologous activated, CAR-transduced T-cells infused in patients with relapsed, refractory Stage IV melanoma	12 months
Imaging studies to measure tumor response	Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.	10 weeks

Collaborators and Investigators

• Sponsor: Gary Doolittle
• Investigators: Principal Investigator: Gary Doolittle, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2016
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): September 13, 2021

Study Registration Dates

• First Submitted: June 18, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimate): June 26, 2015

Study Record Updates

• Last Update Posted (Actual): February 4, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Melanoma; metastatic; relapsed; refractory
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: Mel-2012-01-01