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

NCT00085423 | Completed Phase 2 Results DMC

• 4 other identifiers: CDR0000370788P30CA023108DMS-0320DMS-16531
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma (Skin)

Keywords

recurrent melanoma; stage IV melanoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Number of Participants With Lymphocyte Recovery as Measured by Blood Count

  on days 1-15, weekly for 2 weeks, and then every 2-3 months

• Time to Progression as Measured by RECIST

  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

Study Arms (1)

IL-2, CTX, fludarabine, GM-CSF

EXPERIMENTAL

Aldesleukin (IL-2), cyclophosphamide, fludarabine phosphate, sargramostim

Biological: aldesleukin; Biological: sargramostim; Drug: cyclophosphamide; Drug: fludarabine phosphate

Interventions

aldesleukin BIOLOGICAL

‡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

Also known as: Aldesleukin; IL-2; HD IL-2; Interleukin-2

IL-2, CTX, fludarabine, GM-CSF

sargramostim BIOLOGICAL

GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days.

Also known as: GM-CSF; granulocyte-macrophage colony-stimulating factor

IL-2, CTX, fludarabine, GM-CSF

cyclophosphamide DRUG

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.

Also known as: cyclophosphamide,Cytoxan

IL-2, CTX, fludarabine, GM-CSF

fludarabine phosphate DRUG

Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3

Also known as: Fludara

IL-2, CTX, fludarabine, GM-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Related 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, 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.

  PMID: 20124177 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Interleukin-2; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

This was the first stage of a two-stage phase II study and continuation to next stage required 4 of 18 particpant having an objective response. Only 3 objective responses were noted and the study was terminated at stage 1.

Results Point of Contact

• Title: Dr. Marc Ernstoff
• Organization: Dartmouth-Hitchcock

marc.s.ernstoff@hitchcock.org

603 650 5534

Study Officials

• Marc S. Ernstoff, MD

  Norris Cotton Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: February 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: February 1, 2010
• Last Updated: April 10, 2013
• Results First Posted: April 10, 2013

Record last verified: 2013-04

Locations

US (1)