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

Fred Hutchinson Cancer Center (FHCC)

Status and phase

Completed

Phase 1

Conditions

Melanoma (Skin)

Treatments

Drug: fludarabine phosphate

Biological: therapeutic autologous lymphocytes

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00317759

1796.00

CDR0000327817 (Registry Identifier)

FHCRC-1796.00

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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