Cyclophosphamide and Fludarabine Followed by Cellular Adoptive Immunotherapy and Vaccine Therapy in Patients With Metastatic Melanoma

Phase 1

Completed

• Conditions: Melanoma (Skin)
• Interventions: Biological: Melan-A VLP vaccine, IMP321 adjuvant; Biological: adoptive immunotherapy; Biological: therapeutic autologous lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate

• Registration Number: NCT00324623
• Lead Sponsor: Prof. Serge Leyvraz

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, may be used to prepare the body for other treatments, such as cellular adoptive immunotherapy. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. Giving cyclophosphamide together with fludarabine followed by biological therapy may be an effective treatment for metastatic melanoma.

PURPOSE: This phase I trial is studying the side effects of giving cyclophosphamide together with fludarabine followed by cellular adoptive immunotherapy, and vaccine therapy in treating patients with metastatic melanoma.

Detailed Description

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.

Study Timeline

• Study Start: 2005-09
• Study First Submitted: 2006-05-10
• Study First Submitted QC: 2006-05-10
• Study First Posted: 2006-05-11
• Primary Completion: 2011-11
• Status Verified: 2012-11
• Last Update Submitted: 2012-11-19
• Last Update Posted: 2012-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lymphodepletion, vaccine, IMP321 adjuvant	Melan-A VLP vaccine, IMP321 adjuvant	-
Lymphodepletion, vaccine, IMP321 adjuvant	fludarabine phosphate	-
Lymphodepletion, vaccine, IMP321 adjuvant	adoptive immunotherapy	-
Lymphodepletion, vaccine, IMP321 adjuvant	therapeutic autologous lymphocytes	-
Lymphodepletion, vaccine, IMP321 adjuvant	cyclophosphamide	-

Primary Outcome Measures

Name	Time	Method
Phenotype, function, and T-cell receptor repertoire	Anti-tumor immune response evaluated at each vaccine and until the last administered vaccine
Tumor response	Tumor response evaluated 4 weeks after last vaccine
Toxicity	Within 30 days after completion of the last vaccine

Trial Locations

Locations (1)

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland