Fludarabine Followed By Adoptive Immunotherapy in Treating Patients With Stage IV Melanoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00317759
First received: April 24, 2006
Last updated: May 5, 2010
Last verified: May 2010
  Purpose

RATIONALE: Biological therapies such as cellular adoptive immunotherapy use different ways to stimulate the immune system and stop cancer cells from growing. Fludarabine may help the immune system kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of fludarabine followed by cellular adoptive immunotherapy in treating patients who have metastatic melanoma.


Condition Intervention Phase
Melanoma (Skin)
Biological: therapeutic autologous lymphocytes
Drug: fludarabine phosphate
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Fludarabine Lymphodepletion for Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Estimated Enrollment: 12
Study Start Date: May 2003
Study Completion Date: October 2008
Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and toxicity of adoptive immunotherapy comprising autologous CD8+ antigen-specific cytotoxic T-lymphocyte (CTL) clones after fludarabine in patients with stage IV melanoma.
  • Determine the duration of in vivo persistence of these CTL clones in these patients.

Secondary

  • Determine the antitumor effect of this regimen in these patients.

OUTLINE: This is an open-label, nonrandomized study.

Patients undergo leukapheresis or weekly phlebotomy for the collection of peripheral blood mononuclear cells from which autologous antigen-specific CD8+ cytotoxic T-lymphocyte (CTL) clones are generated. Patients receive autologous antigen-specific CD8+ CTL clones IV over 30-60 minutes on days 0 and 21 in the absence of rapid disease progression or unacceptable toxicity. Patients also receive fludarabine IV once daily on days 14-18.

Patients are followed for up to 1 year.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic melanoma

    • Stage IV disease
  • HLA-A2 or -A3-expressing disease
  • Bidimensionally measurable residual disease by palpation or radiographic imaging (e.g., x-ray or CT scan)
  • No CNS metastases

    • Previously treated CNS involvement allowed provided there is no evidence of CNS disease at least 2 months after completion of therapy

PATIENT CHARACTERISTICS:

Age

  • 18 to 75

Performance status

  • Karnofsky 80-100%

Life expectancy

  • More than 6 months

Hematopoietic

  • Platelet count > 100,000/mm^3
  • Absolute neutrophil count > 2,000/mm^3

Hepatic

  • SGOT no greater than 3 times upper limit of normal
  • Bilirubin no greater than 1.6 mg/dL
  • INR no greater than 1.5 times normal

Renal

  • Creatinine no greater than 2.0 mg/dL OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular

  • No congestive heart failure
  • No clinically significant hypotension
  • No symptoms of coronary artery disease
  • No cardiac arrhythmia by EKG requiring drug therapy

Pulmonary

  • No clinically significant pulmonary dysfunction
  • FEV_1 at least 1.0 L*
  • DLCO at least 45%* NOTE: *For patients with a history of pulmonary dysfunction

Immunologic

  • No active infection
  • No oral temperature greater than 38.2°C within the past 48 hours
  • No systemic infection requiring chronic maintenance or suppressive therapy

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, IV immunoglobulins, expanded polyclonal tumor-infiltrating lymphocytes, or lymphokine-activated killer therapy)

Chemotherapy

  • At least 3 weeks since prior chemotherapy (standard or experimental)

Endocrine therapy

  • No concurrent steroids

Radiotherapy

  • At least 3 weeks since prior radiotherapy

Surgery

  • Not specified

Other

  • At least 3 weeks since prior immunosuppressive therapy
  • No concurrent pentoxifylline
  • No other concurrent investigational agents
  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: NCT00317759

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Cassian Yee, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00317759     History of Changes
Other Study ID Numbers: 1796.00, FHCRC-1796.00, CDR0000327817
Study First Received: April 24, 2006
Last Updated: May 5, 2010
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
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
Fludarabine
Fludarabine phosphate
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014