Chemotherapy and Total-Body Irradiation Followed By Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Vaccine Therapy in Treating Patients With Metastatic Melanoma
| Status: | Archived |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | October 2008 |
Phase II Study of Metastatic Melanoma Using a Chemoradiation Lymphodepleting Conditioning Regimen Followed by Infusion of Anti-Mart-1 and Anti-gp100 TCR-Gene Engineered Lymphocytes and Peptide Vaccines
RATIONALE: Giving chemotherapy and total-body irradiation before an autologous stem cell
transplant stops the growth of tumor cells by stopping them from dividing or killing them.
Giving an infusion of the patient's lymphocytes that have been treated in the laboratory may
stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin
may stimulate lymphocytes to kill tumor cells. Vaccines made from peptides may help the body
build an effective immune response to kill tumor cells. The stem cells are then returned to
the patient to replace the blood-forming cells that were destroyed by the chemotherapy,
radiation therapy, lymphocyte therapy, and vaccine therapy.
PURPOSE: This randomized phase II trial is studying how well giving chemotherapy and
total-body irradiation together with laboratory-treated autologous lymphocytes, aldesleukin,
and vaccine therapy works in treating patients with metastatic melanoma.
OBJECTIVES:
Primary
- Determine if the administration of anti-gp100:154-162 and anti-MART-1:27-35 T-cell
receptor (TCR) gene-engineered peripheral blood lymphocytes (PBL), high-dose
aldesleukin, and gp100:154-162 or MART-1:26-35(27L) peptide vaccination following a
chemoradiation lymphodepleting preparative regimen results in complete clinical tumor
regression in patients with metastatic melanoma (closed as of 09/21/09).
- Determine if the administration of anti-gp100:154-162 and anti-MART-1:27-35 TCR
gene-engineered CD8+ PBL, high-dose aldesleukin, and gp100:154-162 or MART-1:26-35(27L)
peptide vaccination following a chemoradiation lymphodepleting preparative regimen
results in complete clinical tumor regression in patients with metastatic melanoma.
- Determine whether the administration of the specific vaccine (gp100:154-162 or
MART-1:26-35[27L] peptide) can increase the persistence of the specific transferred
cells (anti-gp100:154-162, anti-gp100:154-162 TCR CD8+ PB, anti-MART-1:27-35 TCR PBL,
or anti-MART-1:27-35 TCR CD8+ PBL) in these patients.
Secondary
- Determine the toxicity profile of these treatment regimens in these patients.
OUTLINE:
- Leukapheresis and cell preparation: Patients undergo leukapheresis to obtain stem cells
(for re-infusion after peripheral blood lymphocyte [PBL] therapy) and peripheral blood
mononuclear cells (PBMCs). The PBMCs are cultured in the presence of anti-CD3 (OKT3)
and aldesleukin to stimulate T-cell growth and submitted to CliniMACS microbead for CD8
separation and purification. CD8+ PBL are then transduced by exposure to gp100:154-162
and MART-1 F5 T-cell receptor (TCR) retroviral vectors and expanded in culture.
- Lymphocyte-depleting preparative regimen: Patients receive cyclophosphamide IV over 1
hour on days -6 and -5 and fludarabine phosphate IV over 15-30 minutes on days -6 to
-2. Patients undergo total-body irradiation twice on day -2 and once on day -1.
- Gene-engineered autologous PBL infusion (closed as of 09/21/09): Patients receive
anti-MART-1:27-35 or anti-gp100:154-162 TCR gene-engineered autologous transduced PBL
IV over 20-30 minutes on day 0. Patients also receive filgrastim (G-CSF) subcutaneously
(SC) daily beginning on day 0 or 1 and continuing until blood counts recover.
- Gene-engineered autologous CD8+ peripheral blood lymphocyte infusion: Patients receive
anti-MART-1:27-35 and anti-gp100:154-162 TCR gene-engineered autologous transduced CD8+
PBL IV over 20-30 minutes on day 0. Patients also receive filgrastim (G-CSF)
subcutaneously (SC) daily beginning on day 0 or 1 and continuing until blood counts
recover.
- High-dose aldesleukin: Patients receive high-dose aldesleukin IV over 15 minutes every
8 hours on days 0-4 (maximum of 15 doses).
- Peptide vaccination:Patients are randomized to 1 of 2 peptide vaccination arms.
- Arm I: Patients receive gp100:154-162 peptide vaccine emulsified in incomplete
Freund's adjuvant (IFA) SC on days 0, 7, and 14.
- Arm II: Patients receive MART-1:26-35(27L) peptide vaccine emulsified in IFA SC on
days 0, 7, and 14.
- Autologous stem cell infusion: Patients receive autologous CD34+ selected stem cells IV
on day 1.
Blood samples are collected periodically for immunological monitoring. Samples are analyzed
by PCR, FACS analysis using tetramer staining, immunological assays, and RT-PCR.
After completion of study therapy, patients are followed periodically for up to 15 years.
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