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

Primary Purpose

Melanoma (Skin)

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

therapeutic autologous lymphocytes

Use of an artificial antigen presenting cell (aAPC) to generate CTL

GM-CSF

Irradiation of cutaneous tumor lesion

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring CTL, MART-1, Melan-A, artificial APC, melanoma, metastatic melanoma, adoptive immunotherapy, adoptive cell transfer, immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

Different dose of CTL

Combination of CTL with GMCSF +/- radiation

Outcomes

Primary Outcome Measures

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

Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines

Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy

Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy

Secondary Outcome Measures

Evaluate function, phenotype, and trafficking of infused CTL.

Full Information

NCT ID

NCT00512889

First Posted

August 3, 2007

Last Updated

February 28, 2013

Sponsor

Dana-Farber Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT00512889

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma (Skin)

Keywords

CTL, MART-1, Melan-A, artificial APC, melanoma, metastatic melanoma, adoptive immunotherapy, adoptive cell transfer, immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Different dose of CTL

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

Different dose of CTL

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

Combination of CTL with GMCSF +/- radiation

Intervention Type

Biological

Intervention Name(s)

therapeutic autologous lymphocytes

Intervention Description

Autologous CTL generated from peripheral blood following culture with MART1/Melan-A peptide pulsed aAPC.

Intervention Type

Genetic

Intervention Name(s)

Use of an artificial antigen presenting cell (aAPC) to generate CTL

Intervention Description

A genetically modified artificial antigen presenting cell (aAPC) is used in the generation of anti-tumor CTL.

Intervention Type

Drug

Intervention Name(s)

GM-CSF

Intervention Description

GM-CSF will be used as an immune activator and combined with the infusion of MART1/Melan-A specific CTL.

Intervention Type

Radiation

Intervention Name(s)

Irradiation of cutaneous tumor lesion

Intervention Description

Irradiation of cutaneous melanoma lesion will be combined with the infusion of MART1/Melan-A specific CTL.

Primary Outcome Measure Information:

Title

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

Time Frame

2 years

Title

Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines

Time Frame

2 years

Title

Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy

Time Frame

2 years

Title

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 Measure Information:

Title

Evaluate function, phenotype, and trafficking of infused CTL.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marcus Butler, MD

Organizational Affiliation

Dana-Farber Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21525398

Citation

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.

Results Reference

result

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

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