High Dose Interleukin-2 (IL-2) Therapy In "Lymphodepleted Primed" Patients With Metastatic Melanoma
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
High Dose Interleukin-2 (IL-2) Therapy In "Lymphodepleted Primed" Patients With Metastatic Melanoma
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST
Outcome Description:
Objective response as measured by radiological and physical examination using RECIST criteria.
Outcome Time Frame:
Response at 12 weeks
Safety Issue:
No
Principal Investigator
Marc S. Ernstoff, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Norris Cotton Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000370788
NCT ID:
NCT00085423
Start Date:
February 2004
Completion Date:
February 2010
Related Keywords:
- Melanoma (Skin)
- recurrent melanoma
- stage IV melanoma
- Melanoma
Name | Location |
|---|---|
| Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
