Adoptive Transfer of MART1/Melan-A CTL for Malignant Melanoma - Full Text View

Purpose

RATIONALE: Cytotoxic T lymphocytes (CTL) are cells of the immune system that can fight infections and cancer. These CTL can be manipulated in the laboratory so that they can target an individual's cancer.

PURPOSE: This early phase trial is studying the feasibility and side effects of intravenous infusions of CTL generated in the laboratory. To produce the CTL, the study participant's own immune cells are collected by a procedure called a leukapheresis. The cells then undergo laboratory processing for three weeks. Part of this processing includes mixing the patients immune cells with a new kind of cell that has some extra genes added to it. These extra genes are to "teach" the participant's own immune cells to become anti-tumor CTL that can attack the melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Biological: therapeutic autologous lymphocytes Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL Drug: GM-CSF Radiation: Irradiation of cutaneous tumor lesion	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Pilot Study of the Adoptive Transfer of MART1/Melan-A CTL for Malignant Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Sargramostim

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluate function, phenotype, and trafficking of infused CTL. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	9
Study Start Date:	August 2007
Study Completion Date:	January 2013
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 Different dose of CTL	Biological: therapeutic autologous lymphocytes Autologous CTL generated from peripheral blood following culture with MART1/Melan-A peptide pulsed aAPC. Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL A genetically modified artificial antigen presenting cell (aAPC) is used in the generation of anti-tumor CTL.
Experimental: Cohort 2 Different dose of CTL	Biological: therapeutic autologous lymphocytes Autologous CTL generated from peripheral blood following culture with MART1/Melan-A peptide pulsed aAPC. Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL A genetically modified artificial antigen presenting cell (aAPC) is used in the generation of anti-tumor CTL.
Experimental: Cohort 3 Combination of CTL with GMCSF +/- radiation	Biological: therapeutic autologous lymphocytes Autologous CTL generated from peripheral blood following culture with MART1/Melan-A peptide pulsed aAPC. Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL A genetically modified artificial antigen presenting cell (aAPC) is used in the generation of anti-tumor CTL. Drug: GM-CSF GM-CSF will be used as an immune activator and combined with the infusion of MART1/Melan-A specific CTL. Radiation: Irradiation of cutaneous tumor lesion Irradiation of cutaneous melanoma lesion will be combined with the infusion of MART1/Melan-A specific CTL.

Detailed Description:

DETAILED OUTLINE: This is an early phase pilot/feasibility trial.

Study subjects will be sequentially accrued to three cohorts. Cohorts 1 and 2 will evaluate the safety and feasibility of infusing two different doses of CTL.

Participants in all cohorts will undergo two CTL infusions 5 weeks apart.
Procedures performed during the trial will include physical examinations, laboratory tests, delayed hypersensitivity testing, and skin biopsies.
Between 5 and 8 days after the first CTL infusion, a biopsy or excision of a melanoma lesion may be performed.
Three leukapheresis procedures will be performed: two to collect peripheral blood for CTL production and one for research purposes at the end of the clinical trial.
Radiology tests (including CT scans) will be performed prior to infusion and about 4-5 weeks after the second CTL infusion.

Eligibility

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

Criteria

Inclusion Criteria:

Patients with metastatic melanoma: Either unresectable Stage III or any Stage IV
ECOG of 0 or 1
HLA-A*0201 haplotype
Baseline tumor biopsy MART1/Melan-A expression present (in >10% of tumor cells)
Patient provides consent for all required biopsies
Adequate intravenous access for leukapheresis
Absolute lymphocyte count >500/ul at least once within 30 days of leukapheresis
Life expectancy greater than 4 months in the opinion of the study clinician
Negative pregnancy test

Exclusion Criteria:

Administration of systemic corticosteroids within 28 days of planned leukapheresis
Administration of cytotoxic chemotherapy or anti-tumor immunotherapy within 28 days of planned leukapheresis
Administration of radiotherapy within 28 days of planned leukapheresis with the exception of subjects accrued to Cohort 3
Active autoimmunity requiring systemic immunosuppressive therapy
HIV infection
Previous enrollment on this protocol and infusion of MART1/Melan-A CTL

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00512889

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Dana-Farber Cancer Institute

Investigators

Principal Investigator:

Marcus Butler, MD

Dana-Farber Cancer Institute

More Information

Publications:

Butler MO, Friedlander P, Milstein MI, Mooney MM, Metzler G, Murray AP, Tanaka M, Berezovskaya A, Imataki O, Drury L, Brennan L, Flavin M, Neuberg D, Stevenson K, Lawrence D, Hodi FS, Velazquez EF, Jaklitsch MT, Russell SE, Mihm M, Nadler LM, Hirano N. Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells. Sci Transl Med. 2011 Apr 27;3(80):80ra34. doi: 10.1126/scitranslmed.3002207.

Responsible Party:	Marcus O. Butler, MD, Instructor, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00512889 History of Changes
Other Study ID Numbers:	06-250
Study First Received:	August 3, 2007
Last Updated:	February 28, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

CTL
MART-1
Melan-A
artificial APC
melanoma

metastatic melanoma
adoptive immunotherapy
adoptive cell transfer
immunotherapy

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 21, 2013