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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Marcus O. Butler, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00512889
First received: August 3, 2007
Last updated: February 28, 2013
Last verified: February 2013
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 29, 2014