Gene-Modified T Lymphocytes With or Without Vaccine Therapy and/or Aldesleukin in Treating Patients With High-Risk Melanoma - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00706992

Purpose

RATIONALE: Gene-modified T lymphocytes may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from a peptide may help the body build an effective immune response to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. It is not yet known whether gene-modified T lymphocytes are more effective when given with or without vaccine therapy and/or aldesleukin in treating patients with melanoma.

PURPOSE: This randomized phase II trial is studying how well gene-modified T lymphocytes work when given with or without vaccine therapy and/or aldesleukin in treating patients with high-risk melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Drug: MART-1:26-35(27L) peptide vaccine Drug: aldesleukin Drug: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes Drug: incomplete Freund's adjuvant	Phase II

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Aldesleukin Freund's adjuvant Montanide ISA 51

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Transfer of Autologous T Cells Transduced With the Anti-MART-1 F5 T Cell Receptor in High Risk Melanoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Immunologic response [ Designated as safety issue: No ]

Estimated Enrollment:	156
Study Start Date:	March 2008
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes IV over 20-30 minutes on day 0.	Drug: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes Given IV
Arm II: Experimental Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes as in arm I and MART-1:26-35(27L) peptide vaccine emulsified in Montanide ISA-51 subcutaneously (SC) on days 0 and 30.	Drug: MART-1:26-35(27L) peptide vaccine Given subcutaneously Drug: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes Given IV Drug: incomplete Freund's adjuvant Given subcutaneously
Arm III: Experimental Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes as in arm I and aldesleukin SC on days 0-4.	Drug: aldesleukin Given subcutaneously Drug: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes Given IV
Arm IV: Experimental Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes as in arm I, MART-1:26-35(27L) peptide vaccine emulsified in Montanide ISA-51 as in arm II, and aldesleukin as in arm III.	Drug: MART-1:26-35(27L) peptide vaccine Given subcutaneously Drug: aldesleukin Given subcutaneously Drug: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes Given IV Drug: incomplete Freund's adjuvant Given subcutaneously

Detailed Description:

OBJECTIVES:

To evaluate the ability of four different treatment strategies to enhance the persistence of anti-tumor T cells in the circulation at 5-10 days and at 31-35 days after treatment and potentially select one treatment strategy for further study.

OUTLINE: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMC). PBMCs are then cultured in the presence of anti-CD3 (OKT3) and aldesleukin to stimulate T-cell growth. The T cells are transduced with the anti-MART-1 F5 T-cell receptor (TCR) retroviral vector and then expanded in vitro. Patients are then randomized to 1 of 4 treatment arms.

Arm I: Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes IV over 20-30 minutes on day 0.
Arm II: Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes as in arm I and MART-1:26-35(27L) peptide vaccine emulsified in Montanide ISA-51 subcutaneously (SC) on days 0 and 30.
Arm III: Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes as in arm I and aldesleukin SC on days 0-4.
Arm IV: Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes as in arm I, MART-1:26-35(27L) peptide vaccine emulsified in Montanide ISA-51 as in arm II, and aldesleukin as in arm III.

Patients undergo blood sample collection periodically for immunological correlative studies. Immunological studies include evaluation of precursor frequency by in vitro sensitization assays using the MART-1 peptide and by tetramer analysis; estimation of in vivo survival of lymphocytes derived from the infused cells by tetramer analysis; and measurement of CD4 and CD8 T cells, evaluation of persistence of TCR gene-transduced cells, and detection of replication competent retrovirus (RCR) by PCR.

After completion of study therapy, patients are followed periodically for up to 15 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed high-risk primary cutaneous melanoma meeting any of the following criteria:
- Ulcerated lesions ≥ 2.0 mm in thickness
- Any lesions ≥ 4.0 mm in thickness
- At least 1 positive lymph node
- Local recurrence
- Metastatic disease that was surgically resected within the past 6 months
Clinically disease-free as documented by radiologic studies within the past 6 weeks
HLA-A*0201 positive
No ocular or mucosal melanoma

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
ANC > 1,000/mm³ (without filgrastim [G-CSF] support)
WBC > 3,000/mm³
Platelet count > 90,000/mm³
Hemoglobin > 8.0 g/dL
ALT and AST ≤ 2.5 times upper limit of normal
Total bilirubin ≤ 1.5 mg/dL (< 3.0 mg/dL for patients with Gilbert's syndrome)
Serum creatinine ≤ 1.6 mg/dL
HIV antibody negative
Hepatitis B antigen and hepatitis C antibody negative (unless antigen negative)
No autoimmune disease (e.g., autoimmune colitis or Crohn's disease)
No known immunodeficiency disease (primary or secondary), as evidenced by abnormal WBC count
No active systemic infections, including concurrent opportunistic infections
No known severe hypersensitivity to any of the agents used in this study
No concurrent major medical illnesses
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during study therapy

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior therapy (vitiligo or alopecia allowed)
No prior immunization with MART-1
At least 3 weeks since prior systemic therapy, including adjuvant immunotherapy (e.g., interferon) for melanoma
Prior surgery for melanoma within the past 3 weeks allowed
No concurrent systemic steroid therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706992

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Steven A. Rosenberg, MD, PhD

NCI - Surgery Branch

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000599135, NCI-08-C-0162, NCI-P07309
Study First Received:	June 27, 2008
Last Updated:	December 11, 2008
ClinicalTrials.gov Identifier:	NCT00706992
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II melanoma
stage III melanoma
stage IV melanoma
recurrent melanoma

Study placed in the following topic categories:

Neuroectodermal Tumors
Aldesleukin
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma

Freund's Adjuvant
Nevus
Recurrence
Neuroendocrine Tumors
Melanoma

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplasms by Histologic Type
Anti-HIV Agents
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs

Adjuvants, Immunologic
Antiviral Agents
Pharmacologic Actions
Neoplasms
Anti-Retroviral Agents
Therapeutic Uses
Nevi and Melanomas

ClinicalTrials.gov processed this record on January 16, 2009