Clinical Trials /

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

NCT02482532

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Mel-2012-01-01
  • NCT ID: NCT02482532

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
tvs-CTL Vaccinetvs-CTL Vaccine

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
tvs-CTL VaccineExperimentalInfusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.
  • tvs-CTL Vaccine

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)
      
Maximum Eligible Age:66 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measurement of infusion related adverse events to evaluate the safety of infused T-cells
Time Frame:4 weeks
Safety Issue:
Description:To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)

Secondary Outcome Measures

Measure:PCR measurement of retroviral construct to measure the expansion of infused T-cells
Time Frame:12 months
Safety Issue:
Description:To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines
Measure:PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination
Time Frame:12 months
Safety Issue:
Description: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
Measure:Imaging studies to measure tumor response
Time Frame:10 weeks
Safety Issue:
Description:Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gary Doolittle

Trial Keywords

  • Melanoma
  • metastatic
  • relapsed
  • refractory

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