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

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00512889

Collaborator

(none)

Enrollment

Location

Arms

65.1

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

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 :

Aug 1, 2007

Actual Primary Completion Date :

Feb 1, 2011

Actual Study Completion Date :

Jan 1, 2013

Arms and Interventions

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.

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

Primary Outcome Measures

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

Secondary Outcome Measures

Evaluate function, phenotype, and trafficking of infused CTL. [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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