Cyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma

Dartmouth Health

Status and phase

Completed

Phase 2

Conditions

Melanoma (Skin)

Treatments

Biological: sargramostim

Drug: fludarabine phosphate

Biological: aldesleukin

Drug: cyclophosphamide

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00085423

DMS-0320 (Other Identifier)

DMS-16531 (Other Identifier)

P30CA023108 (U.S. NIH Grant/Contract)

CDR0000370788

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with high-dose interleukin-2 works in treating patients with metastatic melanoma.

Full description

OBJECTIVES:

Primary

Determine the objective response rate in lymphodepleted patients with metastatic melanoma treated with cyclophosphamide, fludarabine, and high-dose interleukin-2.
Determine the feasibility of this regimen in these patients.

Secondary

Determine the quality and quantity of lymphocyte recovery in these patients during and after treatment with this regimen.
Determine time to disease progression and survival in patients treated with this regimen.

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

Patients receive lymphodepleting therapy comprising cyclophosphamide IV over 1 hour on days 1 and 2 and fludarabine IV over 30 minutes on days 3-7. Patients then receive high-dose interleukin-2 IV every 8 hours (14 doses) on days 8-12 and 22-26. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 8 and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study.

Enrollment

20 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed melanoma
Metastatic disease
Measurable disease
No history of brain metastases
Over 18
Karnofsky 60-100%
Life expectancy At least 12 weeks
Hematopoietic
Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 75,000/mm^3
Hemoglobin ≥ 8.5 g/dL
aspartate aminotransferase ≤ 2 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
Bilirubin ≤ 2 times ULN (except for patients with Gilbert's syndrome)
Hepatitis B and C negative
Creatinine ≤ 2.0 times ULN
Creatinine clearance ≥ 50 mL/min
Cardiovascular
Ejection fraction ≥ 50%
No evidence of congestive heart failure
No symptoms of coronary artery disease
No serious cardiac arrhythmias
No myocardial infarction within the past 6 months
Cardiac stress test negative or of low probability for patients > 40 years of age OR who have had prior myocardial infarction > 6 months ago
Pulmonary Forced expiratory volume 1 ≥ 2.0 liters OR at least 75% of predicted for height and age
Diffusing capacity of lung for carbon monoxide ≥ 60%
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative

Exclusion criteria

No uncontrolled diabetes
No history of autoimmune disease
No active infection
No other concurrent significant illness that would preclude study participation
No other malignancy within the past 5 years except nonmelanoma skin cancer or non-invasive cancer (e.g., carcinoma in situ of the cervix, superficial bladder cancer without local recurrence, or carcinoma in situ of the breast)
At least 4 weeks since prior immunotherapy and recovered
No other concurrent anticancer biologic agents
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
No concurrent chemotherapy
At least 4 weeks since prior steroid therapy
No concurrent corticosteroids
At least 4 weeks since prior radiotherapy and recovered
No concurrent radiotherapy
At least 4 weeks since prior surgery and recovered
No concurrent immunosuppressive therapy