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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00317759
Recruitment Status : Completed
First Posted : April 25, 2006
Last Update Posted : October 1, 2015
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Center

Tracking Information
First Submitted Date  ICMJE April 24, 2006
First Posted Date  ICMJE April 25, 2006
Last Update Posted Date October 1, 2015
Study Start Date  ICMJE May 2003
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Fludarabine Followed By Adoptive Immunotherapy in Treating Patients With Stage IV Melanoma
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description



  • 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.


  • 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma (Skin)
Intervention  ICMJE
  • Biological: therapeutic autologous lymphocytes
  • Drug: fludarabine phosphate
Study Arms  ICMJE Not Provided
Publications * Wallen H, Thompson JA, Reilly JZ, Rodmyre RM, Cao J, Yee C. Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma. PLoS One. 2009;4(3):e4749. doi: 10.1371/journal.pone.0004749. Epub 2009 Mar 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: February¬†8,¬†2007)
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE October 2008
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE


  • 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



  • 18 to 75

Performance status

  • Karnofsky 80-100%

Life expectancy

  • More than 6 months


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


  • 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


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


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


  • 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


  • 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


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


Biologic therapy

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


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

Endocrine therapy

  • No concurrent steroids


  • At least 3 weeks since prior radiotherapy


  • Not specified


  • At least 3 weeks since prior immunosuppressive therapy
  • No concurrent pentoxifylline
  • No other concurrent investigational agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00317759
Other Study ID Numbers  ICMJE 1796.00
CDR0000327817 ( Registry Identifier: PDQ )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Not Provided
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Fred Hutchinson Cancer Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Cassian Yee, MD Fred Hutchinson Cancer Center
PRS Account Fred Hutchinson Cancer Center
Verification Date May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP