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

Phase 1

Completed

• Conditions: Melanoma (Skin)
• Interventions: 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

• Registration Number: NCT00512889
• Lead Sponsor: Dana-Farber Cancer Institute

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.

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 Timeline

• Study Start: 2007-08
• Study First Submitted: 2007-08-03
• Study First Submitted QC: 2007-08-07
• Study First Posted: 2007-08-08
• Primary Completion: 2011-02
• Study Completion: 2013-01
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-28
• Last Update Posted: 2013-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2	Use of an artificial antigen presenting cell (aAPC) to generate CTL	Different dose of CTL
Cohort 1	therapeutic autologous lymphocytes	Different dose of CTL
Cohort 2	therapeutic autologous lymphocytes	Different dose of CTL
Cohort 3	Irradiation of cutaneous tumor lesion	Combination of CTL with GMCSF +/- radiation
Cohort 3	therapeutic autologous lymphocytes	Combination of CTL with GMCSF +/- radiation
Cohort 1	Use of an artificial antigen presenting cell (aAPC) to generate CTL	Different dose of CTL
Cohort 3	Use of an artificial antigen presenting cell (aAPC) to generate CTL	Combination of CTL with GMCSF +/- radiation
Cohort 3	GM-CSF	Combination of CTL with GMCSF +/- radiation

Primary Outcome Measures

Name	Time	Method
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
Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population	2 years

Secondary Outcome Measures

Name	Time	Method
Evaluate function, phenotype, and trafficking of infused CTL.	2 years

Trial Locations

Locations (1)

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States