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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00085423
First received: June 10, 2004
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Biological: aldesleukin
Biological: sargramostim
Drug: cyclophosphamide
Drug: fludarabine phosphate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Interleukin-2 (IL-2) Therapy In "Lymphodepleted Primed" Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST [ Time Frame: Response at 12 weeks ] [ Designated as safety issue: No ]
    Objective response as measured by radiological and physical examination using RECIST criteria.


Secondary Outcome Measures:
  • Number of Participants With Lymphocyte Recovery as Measured by Blood Count [ Time Frame: on days 1-15, weekly for 2 weeks, and then every 2-3 months ] [ Designated as safety issue: No ]
    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.

  • Time to Progression as Measured by RECIST [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Clinical outcome used the National Cancer Institute's Response Evaluation Criteria in Solid Tumors (RECIST)1.0.


Enrollment: 20
Study Start Date: February 2004
Study Completion Date: February 2010
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IL-2, CTX, fludarabine, GM-CSF
Aldesleukin (IL-2), cyclophosphamide, fludarabine phosphate, sargramostim
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
Other Name: Aldesleukin; IL-2; HD IL-2; Interleukin-2
Biological: sargramostim
GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days.
Other Name: GM-CSF; granulocyte-macrophage colony-stimulating factor
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.
Other Name: cyclophosphamide,Cytoxan
Drug: fludarabine phosphate
Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3
Other Name: Fludara

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085423

Locations
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Study Chair: Marc S. Ernstoff, MD Norris Cotton Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00085423     History of Changes
Obsolete Identifiers: NCT00225771
Other Study ID Numbers: CDR0000370788, P30CA023108, DMS-0320, DMS-16531
Study First Received: June 10, 2004
Results First Received: January 26, 2012
Last Updated: April 9, 2013
Health Authority: United States: Federal Government

Keywords provided by Dartmouth-Hitchcock Medical Center:
recurrent melanoma
stage IV melanoma

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Aldesleukin
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Interleukin-2
Vidarabine
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Central Nervous System Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 20, 2014