We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02482532
Recruitment Status : Completed
First Posted : June 26, 2015
Last Update Posted : February 4, 2022
Sponsor:
Information provided by (Responsible Party):
Gary Doolittle, University of Kansas Medical Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Melanoma Biological: tvs-CTL Vaccine Phase 1

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Vaccine Enriched, Autologous, Activated T-Cells Redirected to the Tumor Marker GD2 in Patients With Relapsed/Refractory Melanoma
Actual Study Start Date : October 6, 2016
Actual Primary Completion Date : October 10, 2019
Actual Study Completion Date : September 13, 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma Vaccines

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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)


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Measurement of infusion related adverse events to evaluate the safety of infused T-cells [ Time Frame: 4 weeks ]
    To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)

  2. PCR measurement of retroviral construct to measure persistence of infused T-cells [ Time Frame: 4 weeks ]
    To evaluate how long the infused T-cells remain in the blood stream

  3. Measurement of replication competent retrovirus to evaluate the safety of infused T-cells [ Time Frame: 4 weeks ]
    To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)


Secondary Outcome Measures :
  1. PCR measurement of retroviral construct to measure the expansion of infused T-cells [ Time Frame: 12 months ]
    To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines

  2. PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination [ Time Frame: 12 months ]
    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

  3. Imaging studies to measure tumor response [ Time Frame: 10 weeks ]
    Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 66 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02482532


Locations
Layout table for location information
United States, Kansas
KU Cancer Center
Fairway, Kansas, United States, 66205
Sponsors and Collaborators
Gary Doolittle
Investigators
Layout table for investigator information
Principal Investigator: Gary Doolittle, MD University of Kansas Medical Center
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Gary Doolittle, Professor, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT02482532    
Other Study ID Numbers: Mel-2012-01-01
First Posted: June 26, 2015    Key Record Dates
Last Update Posted: February 4, 2022
Last Verified: November 2021
Keywords provided by Gary Doolittle, University of Kansas Medical Center:
Melanoma
metastatic
relapsed
refractory
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas