Clinical trial NCT00085423: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: recurrent melanoma
stage IV melanoma
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST
timeFrame: Response at 12 weeks
Secondary outcomes:
measure: Number of Participants With Lymphocyte Recovery as Measured by Blood Count
timeFrame: on days 1-15, weekly for 2 weeks, and then every 2-3 months
measure: Time to Progression as Measured by RECIST
timeFrame: 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
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Norris Cotton Cancer Center
name: Marc S. Ernstoff, MD
role: STUDY_CHAIR
References:
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.