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

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ClinicalTrials.gov Identifier: NCT02482532
Recruitment Status : Recruiting
First Posted : June 26, 2015
Last Update Posted : November 18, 2016
Sponsor:
Information provided by (Responsible Party):
Gary Doolittle, University of Kansas Medical Center

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3 participants
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
Study Start Date : January 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2035

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

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)




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.



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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)

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


Contacts
Contact: Gary Doolittle, MD 913-588-6029 gdoolitt@kumc.edu
Contact: Kerry Hepler, RN 913-945-7552 khepler@kumc.edu

Locations
United States, Kansas
KU Cancer Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Gary Doolittle, MD    913-588-6029    gdoolitt@kumc.edu   
Contact: Kerry Hepler, RN    913-945-7552    khepler@Kumc.edu   
Sponsors and Collaborators
Gary Doolittle
Investigators
Principal Investigator: Gary Doolittle, MD University of Kansas Medical Center

Responsible Party: Gary Doolittle, Professor, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT02482532     History of Changes
Other Study ID Numbers: Mel-2012-01-01
First Posted: June 26, 2015    Key Record Dates
Last Update Posted: November 18, 2016
Last Verified: November 2016

Keywords provided by Gary Doolittle, University of Kansas Medical Center:
Melanoma
metastatic
relapsed
refractory

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vaccines
Immunologic Factors
Physiological Effects of Drugs