Clinical trial NCT00317759: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-04-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Cassian Yee, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.