Clinical trial NCT00512889: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma (Skin)
Keywords: CTL
MART-1
Melan-A
artificial APC
melanoma
metastatic melanoma
adoptive immunotherapy
adoptive cell transfer
immunotherapy
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2007-08-08
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population
timeFrame: 2 years
measure: Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines
timeFrame: 2 years
measure: Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
timeFrame: 2 years
measure: Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
timeFrame: 2 years
Secondary outcomes:
measure: Evaluate function, phenotype, and trafficking of infused CTL.
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Marcus Butler, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.