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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| tvs-CTL Vaccine | | tvs-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
| Name | Type | Description | Interventions |
|---|
| tvs-CTL Vaccine | Experimental | Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells. | |
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
Last Updated
November 18, 2016
