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

Primary Purpose

Melanoma (Skin)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
therapeutic autologous lymphocytes
fludarabine phosphate
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage IV melanoma, recurrent melanoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
April 24, 2006
Last Updated
September 30, 2015
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00317759
Brief Title
Fludarabine Followed By Adoptive Immunotherapy in Treating Patients With Stage IV Melanoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2010
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin)
Keywords
stage IV melanoma, recurrent melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
therapeutic autologous lymphocytes
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cassian Yee, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19270751
Citation
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.
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Fludarabine Followed By Adoptive Immunotherapy in Treating Patients With Stage IV Melanoma

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