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Phase I Study of In Vivo Expansion of Melan-A/MART-1 Antigen-Specific CD8 T Lymphocytes Following Transient Immunosuppression in Patients With Advanced Melanoma


Phase 1
18 Years
75 Years
Not Enrolling
Both
Melanoma (Skin)

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Trial Information

Phase I Study of In Vivo Expansion of Melan-A/MART-1 Antigen-Specific CD8 T Lymphocytes Following Transient Immunosuppression in Patients With Advanced Melanoma


OBJECTIVES:

- Determine the magnitude and duration of the expansion of antigen-specific T-cells
present in post-vaccination peripheral blood mononuclear cells and reinfused after
immunosuppression in patients with metastatic melanoma.

- Characterize the T-cell subsets (phenotype, function, T-cell receptor repertoire) in
these patients.

- Determine the tumor response in patients treated with this regimen.

- Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label dose-finding study. Patients undergo leukapheresis to collect
whole peripheral blood mononuclear cells (PBMC). Patients are then assigned to 1 of 3
treatment groups.

- Group 1 (closed to accrual as of 5/8/2007): Patients receive cyclophosphamide IV on
days -7 and -6 and fludarabine IV on days -5 to -3. Patients undergo autologous PBMC
infusion on day 0. Patients also receive vaccination comprising Melan-A vaccine
emulsified in incomplete Freund's adjuvant (IFA) subcutaneously (SC) once every 3 weeks
beginning on day 0.

- Group 2 (closed to accrual as of 8/15/2007): Patients receive cyclophosphamide IV at a
higher dose than in group 1 on days -7 and -6 and fludarabine IV on days -5 to -3.
Patients also receive an autologous PBMC infusion and Melan-A vaccine emulsified in IFA
as in group 1.

- Group 3: Patients receive cyclophosphamide IV at 30 mg/kg on days -7 and -6. Patients
also receive fludarabine 30 mg/m2 IV on days -5 to -3, autologous PBMC infusion on day
0,and Melan-A vaccine emulsified in IFA and IMP321. The first 3 patients receive 25
micrograms of IMP321, in the absence of severe 3 or 4 toxicity, the dose will be
escalated to IMP321 250 micrograms.

PROJECTED ACCRUAL: A total of 9 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of metastatic melanoma

- Progressive disease after receiving prior Melan-A peptide vaccine on an immunotherapy
protocol of the Ludwig Institute AND achieved a detectable immune response (increase
of specific CD8^+ TET^+ Melan-A)

- Tumor must express MART-1/Melan-A antigen

- HLA-A2 positive

- Not eligible for other protocols due to progressive disease OR maximum number of
vaccine injections with stable disease has been attained

PATIENT CHARACTERISTICS:

- Performance status 0-2

- Whole blood counts normal

- Pulmonary status normal

- Transaminases < 1.5 times upper limit of normal (ULN)

- Gamma-glutamyl-transferase < 1.5 times ULN

- Bilirubin normal

- Creatinine clearance > 70 mL/min

- No major uncontrolled heart disease

- No arterial hypertension

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Prior chemotherapy, biologic therapy, radiotherapy, and/or surgery allowed

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phenotype, function, and T-cell receptor repertoire

Outcome Time Frame:

Anti-tumor immune response evaluated at each vaccine and until the last administered vaccine

Safety Issue:

No

Principal Investigator

Serge Leyvraz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Centre Hospitalier Universitaire Vaudois

Authority:

Switzerland: Swissmedic

Study ID:

CDR0000468827

NCT ID:

NCT00324623

Start Date:

September 2005

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma

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