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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prof. Serge Leyvraz, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT00324623
First received: May 10, 2006
Last updated: November 19, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Biological: Melan-A VLP vaccine, IMP321 adjuvant
Biological: adoptive immunotherapy
Biological: therapeutic autologous lymphocytes
Drug: cyclophosphamide
Drug: fludarabine phosphate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • Phenotype, function, and T-cell receptor repertoire [ Time Frame: Anti-tumor immune response evaluated at each vaccine and until the last administered vaccine ] [ Designated as safety issue: No ]
  • Tumor response [ Time Frame: Tumor response evaluated 4 weeks after last vaccine ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Within 30 days after completion of the last vaccine ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: September 2005
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lymphodepletion, vaccine, IMP321 adjuvant Biological: Melan-A VLP vaccine, IMP321 adjuvant Biological: adoptive immunotherapy Biological: therapeutic autologous lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324623

Locations
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Sponsors and Collaborators
Prof. Serge Leyvraz
Investigators
Study Chair: Serge Leyvraz, MD Centre Hospitalier Universitaire Vaudois
  More Information

Additional Information:
No publications provided by Centre Hospitalier Universitaire Vaudois

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Serge Leyvraz, Chef de Service, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT00324623     History of Changes
Other Study ID Numbers: CDR0000468827, CHUV-CEPO-ITA-02, EU-20607
Study First Received: May 10, 2006
Last Updated: November 19, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Centre Hospitalier Universitaire Vaudois:
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014