Back to resultsCyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma
Primary Purpose
Melanoma (Skin)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
aldesleukin
sargramostim
cyclophosphamide
fludarabine phosphate
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma (Skin) focused on measuring recurrent melanoma, stage IV melanoma
Eligibility 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
Sites / Locations
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IL-2, CTX, fludarabine, GM-CSF
Arm Description
Aldesleukin (IL-2), cyclophosphamide, fludarabine phosphate, sargramostim
Outcomes
Primary Outcome Measures
Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST
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
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
Clinical outcome used the National Cancer Institute's Response Evaluation Criteria in Solid Tumors (RECIST)1.0.
Full Information
NCT ID
NCT00085423
First Posted
June 10, 2004
Last Updated
April 9, 2013
Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00085423
Brief Title
Cyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma
Official Title
High Dose Interleukin-2 (IL-2) Therapy In "Lymphodepleted Primed" Patients With Metastatic Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
February 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin)
Keywords
recurrent melanoma, stage IV melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IL-2, CTX, fludarabine, GM-CSF
Arm Type
Experimental
Arm Description
Aldesleukin (IL-2), cyclophosphamide, fludarabine phosphate, sargramostim
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
Aldesleukin; IL-2; HD IL-2; Interleukin-2
Intervention Description
‡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
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF; granulocyte-macrophage colony-stimulating factor
Intervention Description
GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
cyclophosphamide,Cytoxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3
Primary Outcome Measure Information:
Title
Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST
Description
Objective response as measured by radiological and physical examination using RECIST criteria.
Time Frame
Response at 12 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Lymphocyte Recovery as Measured by Blood Count
Description
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 Frame
on days 1-15, weekly for 2 weeks, and then every 2-3 months
Title
Time to Progression as Measured by RECIST
Description
Clinical outcome used the National Cancer Institute's Response Evaluation Criteria in Solid Tumors (RECIST)1.0.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc S. Ernstoff, MD
Organizational Affiliation
Norris Cotton Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0002
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20124177
Citation
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, interleukin-2, and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma: clinical outcomes and peripheral-blood cell recovery. J Clin Oncol. 2010 Mar 1;28(7):1196-202. doi: 10.1200/JCO.2009.24.8153. Epub 2010 Feb 1.
Results Reference
result
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Cyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma
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