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

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
tvs-CTL Vaccine
Sponsored by
Gary Doolittle
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Melanoma, metastatic, relapsed, refractory

Eligibility Criteria

18 Years - 66 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • KU Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

tvs-CTL Vaccine

Arm Description

Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.

Outcomes

Primary Outcome Measures

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)
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
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)

Secondary Outcome Measures

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
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
Imaging studies to measure tumor response
Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.

Full Information

First Posted
June 18, 2015
Last Updated
January 20, 2022
Sponsor
Gary Doolittle
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1. Study Identification

Unique Protocol Identification Number
NCT02482532
Brief Title
Vaccine Enriched, Autologous, Activated T-Cells Directed to Tumor in Patients With Relapsed/Refractory Melanoma
Acronym
MARVSmALo
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 Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
October 6, 2016 (Actual)
Primary Completion Date
October 10, 2019 (Actual)
Study Completion Date
September 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Gary Doolittle

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Melanoma, metastatic, relapsed, refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tvs-CTL Vaccine
Arm Type
Experimental
Arm Description
Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.
Intervention Type
Biological
Intervention Name(s)
tvs-CTL Vaccine
Intervention Description
autologous, 14g2a.zeta chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)
Primary Outcome Measure Information:
Title
Measurement of infusion related adverse events to evaluate the safety of infused T-cells
Description
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
Time Frame
4 weeks
Title
PCR measurement of retroviral construct to measure persistence of infused T-cells
Description
To evaluate how long the infused T-cells remain in the blood stream
Time Frame
4 weeks
Title
Measurement of replication competent retrovirus to evaluate the safety of infused T-cells
Description
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
PCR measurement of retroviral construct to measure the expansion of infused T-cells
Description
To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines
Time Frame
12 months
Title
PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination
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
Time Frame
12 months
Title
Imaging studies to measure tumor response
Description
Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.
Time Frame
10 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
66 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Doolittle, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
KU Cancer Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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