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

Melanoma (Skin) Clinical Trial

Official title:

High Dose Interleukin-2 (IL-2) Therapy In "Lymphodepleted Primed" Patients With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00085423
• Other study ID #: CDR0000370788
• Secondary ID: P30CA023108DMS-0
• Status: Completed
• Phase: Phase 2
• First received: June 10, 2004
• Last updated: April 9, 2013
• Start date: February 2004
• Est. completion date: February 2010

Study information

• Verified date: April 2013
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00225771

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 2010
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• aldesleukin
‡Interleukin-2 (aldesleukin) IV (600,000 U/kg; Chiron, Emeryville, CA): two 5-day courses on days 8 and 22. Interleukin-2 was given over 15 minutes every 8 hours. Goal is 14 doses/5-day course
• sargramostim
GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days.

Drug:
• cyclophosphamide
Cyclophosphamide (60 mg/kg/d; Baxter, Deerfield, IL) intravenously (IV) for 2 days with sodium 2- mercaptoethanesulfonate (Mesna; Sicor, Irvine, CA) at 20% of cyclophosphamide dose IV 15 minutes before and 40% of the cyclophosphamide dose orally at 2 and 6 hours after the initiation of chemotherapy.
• fludarabine phosphate
Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3

Locations

Country	Name	City	State
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Gunturu KS, Meehan KR, Mackenzie TA, Crocenzi TS, McDermott D, Usherwood EJ, Margolin KA, Crosby NA, Atkins MB, Turk MJ, Ahonen C, Fuse S, Clark JI, Fisher JL, Noelle RJ, Ernstoff MS. Cytokine working group study of lymphodepleting chemotherapy, interleuk — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST	Objective response as measured by radiological and physical examination using RECIST criteria.	Response at 12 weeks	No
Secondary	Number of Participants With Lymphocyte Recovery as Measured by Blood Count	Lymphocyte recovery to a greater than 1000 cells/mcL was determined by differential peripheral blood cell counts on sequential days as noted in time frame.	on days 1-15, weekly for 2 weeks, and then every 2-3 months	No
Secondary	Time to Progression as Measured by RECIST	Clinical outcome used the National Cancer Institute's Response Evaluation Criteria in Solid Tumors (RECIST)1.0.	From date of randomization until the first date of documented progression or date of death from any cause, which ever came first, assessed up till 100 months	No