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CompletedNCT00324623Updated Nov 20, 2012

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

A Phase 1 interventional study of Melan-A VLP vaccine, IMP321 adjuvant and adoptive immunotherapy in Melanoma (Skin), sponsored by Prof. Serge Leyvraz. Completed at 1 site in Switzerland. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2012-11-20.

Sponsored by Prof. Serge Leyvraz · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
8
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Melanoma (Skin)

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Keywords

  • stage IV melanoma
  • recurrent melanoma
03

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 8 is below the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

This is the only study on the registry with Prof. Serge Leyvraz as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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
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Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
8 participants (actual)

Study arms

  • Experimental
    Lymphodepletion, vaccine, IMP321 adjuvant

    Biological: Melan-A VLP vaccine, IMP321 adjuvant · Biological: adoptive immunotherapy · Biological: therapeutic autologous lymphocytes · Drug: cyclophosphamide · Drug: fludarabine phosphate

Interventions

  • BiologicalMelan-A VLP vaccine, IMP321 adjuvant
  • Biologicaladoptive immunotherapy
  • Biologicaltherapeutic autologous lymphocytes
  • Drugcyclophosphamide
  • Drugfludarabine phosphate
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What researchers measure

Primary outcomes

  1. Phenotype, function, and T-cell receptor repertoire

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

  2. Tumor response

    Time frame: Tumor response evaluated 4 weeks after last vaccine

  3. Toxicity

    Time frame: Within 30 days after completion of the last vaccine

07

Study locations

1 site
  • Centre Hospitalier Universitaire Vaudois
    Lausanne, CH-1011, Switzerland
08

References and documents

Publications

  • Romano E, Michielin O, Voelter V, Laurent J, Bichat H, Stravodimou A, Romero P, Speiser DE, Triebel F, Leyvraz S, Harari A. MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial. J Transl Med. 2014 Apr 12;12:97. doi: 10.1186/1479-5876-12-97. PubMed 24726012 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 20, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00324623
Lead sponsor
Prof. Serge Leyvraz
Responsible party
Prof. Serge Leyvraz (Chef de Service, Centre Hospitalier Universitaire Vaudois) — Sponsor-investigator
First posted
May 11, 2006
Start date
Sep 2005
Primary completion
Nov 2011
Last update
Nov 20, 2012

Study contacts

Serge Leyvraz, MD
study chair · Centre Hospitalier Universitaire Vaudois

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Nov 2012. You cannot join it, but the record below documents what was studied.

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