NCT00512889

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Aug 2007

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2007

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

August 3, 2007

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 8, 2007

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
Last Updated

March 1, 2013

Status Verified

February 1, 2013

Enrollment Period

3.5 years

First QC Date

August 3, 2007

Last Update Submit

February 28, 2013

Conditions

Keywords

CTLMART-1Melan-Aartificial APCmelanomametastatic melanomaadoptive immunotherapyadoptive cell transferimmunotherapy

Outcome Measures

Primary Outcomes (4)

  • 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 Outcomes (1)

  • Evaluate function, phenotype, and trafficking of infused CTL.

    2 years

Study Arms (3)

Cohort 1

EXPERIMENTAL

Different dose of CTL

Biological: therapeutic autologous lymphocytesGenetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL

Cohort 2

EXPERIMENTAL

Different dose of CTL

Biological: therapeutic autologous lymphocytesGenetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL

Cohort 3

EXPERIMENTAL

Combination of CTL with GMCSF +/- radiation

Biological: therapeutic autologous lymphocytesGenetic: Use of an artificial antigen presenting cell (aAPC) to generate CTLDrug: GM-CSFRadiation: Irradiation of cutaneous tumor lesion

Interventions

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

Cohort 1Cohort 2Cohort 3

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

Cohort 1Cohort 2Cohort 3
GM-CSFDRUG

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

Cohort 3

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

Cohort 3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related 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. 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.

MeSH Terms

Conditions

Melanoma

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Study Officials

  • Marcus Butler, MD

    Dana-Farber Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Instructor

Study Record Dates

First Submitted

August 3, 2007

First Posted

August 8, 2007

Study Start

August 1, 2007

Primary Completion

February 1, 2011

Study Completion

January 1, 2013

Last Updated

March 1, 2013

Record last verified: 2013-02

Locations