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

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ClinicalTrials.gov Identifier: NCT00512889
Recruitment Status : Completed
First Posted : August 8, 2007
Last Update Posted : March 1, 2013
Sponsor:
Information provided by (Responsible Party):
Marcus O. Butler, MD, Dana-Farber Cancer Institute

Study Description
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Brief Summary:

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 or disease Intervention/treatment 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

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of the Adoptive Transfer of MART1/Melan-A CTL for Malignant Melanoma
Study Start Date : August 2007
Actual Primary Completion Date : February 2011
Actual Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population [ Time Frame: 2 years ]
  2. Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines [ Time Frame: 2 years ]
  3. Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy [ Time Frame: 2 years ]
  4. Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Evaluate function, phenotype, and trafficking of infused CTL. [ Time Frame: 2 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00512889


Locations
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United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
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Principal Investigator: Marcus Butler, MD Dana-Farber Cancer Institute
More Information
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Publications of Results:

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Responsible Party: Marcus O. Butler, MD, Instructor, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00512889    
Other Study ID Numbers: 06-250
First Posted: August 8, 2007    Key Record Dates
Last Update Posted: March 1, 2013
Last Verified: February 2013
Keywords provided by Marcus O. Butler, MD, Dana-Farber Cancer Institute:
CTL
MART-1
Melan-A
artificial APC
melanoma
 metastatic melanoma
adoptive immunotherapy
adoptive cell transfer
immunotherapy
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas