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

Melanoma (Skin) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00512889
• Other study ID #: 06-250
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2007
• Last updated: February 28, 2013
• Start date: August 2007
• Est. completion date: January 2013

Study information

• Verified date: February 2013
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: January 2013
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

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.

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Es — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population		2 years	No
Primary	Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines		2 years	Yes
Primary	Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy		2 years	No
Primary	Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy		2 years	Yes
Secondary	Evaluate function, phenotype, and trafficking of infused CTL.		2 years	No