Monoclonal Antibody Therapy and Interleukin-2 in Treating Patients With Metastatic Melanoma

June 18, 2013 updated by: National Cancer Institute (NCI)

MDX-CTLA4 Combined With IL-2 for Patients With Metastatic Melanoma

RATIONALE: Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop tumor cells from growing. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining monoclonal antibody therapy with interleukin-2 may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining monoclonal antibody therapy with interleukin-2 in treating patients who have metastatic melanoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose (MTD) of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) in combination with high-dose interleukin-2 (IL-2) in patients with metastatic melanoma. (Phase I is closed to accrual as of 4/13/2004).
Determine the activity of MDX-CTLA4 administered at the MTD with high-dose IL-2 in these patients.
Determine whether the administration of IL-2 alters the pharmacokinetics of MDX-CTLA4 in these patients.
Determine the safety and adverse event profile of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4).

Phase I: Patients receive MDX-CTLA4 IV on days 0, 21, and 42. Patients also receive high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours for up to 15 doses beginning on days 22 and 43. Treatment repeats every 63 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with an ongoing partial response and no greater than grade 1 toxicity may receive additional courses of therapy. Patients who require discontinuation of MDX-CTLA4 due to toxicity may continue receiving IL-2 at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I is closed to accrual as of 4/13/2004).

Phase II: Patients receive treatment as in phase I at the MTD of MDX-CTLA4. Patients who achieve a partial or complete response and later develop recurrent or progressive disease may be retreated at the same dose.

Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-51 patients (3-18 for phase I and 19-33 for phase II) will be accrued for this study within 1 year. (Phase I is closed to accrual as of 4/13/2004).

Study Type

Interventional

Phase

Phase 2
Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Maryland
  - Bethesda, Maryland, United States, 20892-1182
    - Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Histologically confirmed stage IV melanoma
- Mucosal or ocular melanoma also eligible
Clinically evaluable disease
- At least 1 site of measurable disease

PATIENT CHARACTERISTICS:

Age

16 and over

Performance status

ECOG 0-1

Life expectancy

At least 3 months

Hematopoietic

WBC at least 2,500/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL
Hematocrit at least 30%

Hepatic

Bilirubin no greater than upper limit of normal (ULN)* (less than 3.0 mg/dL in patients with Gilbert's syndrome)
AST no greater than 3 times ULN*
Hepatitis B surface antigen negative
Hepatitis C antibody nonreactive
No evidence or history of significant hepatic disease that would preclude safe administration of high-dose IL-2 NOTE: *Unless attributable to disease

Renal

Creatinine no greater than 2.0 mg/dL
No evidence or history of significant renal disease that would preclude safe administration of high-dose IL-2

Cardiovascular

No evidence or history of significant cardiac disease that would preclude safe administration of high-dose IL-2
Thallium stress test normal (for patients over 50 years of age or with a history of cardiovascular disease)

Pulmonary

No evidence or history of significant pulmonary disease that would preclude safe administration of high-dose IL-2

Immunologic

HIV negative
No autoimmune disease (including uveitis and autoimmune inflammatory eye disease)
No active infection

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
No evidence or history of significant gastrointestinal disease that would preclude safe administration of high-dose IL-2
No evidence or history of psychiatric disease that would preclude safe administration of high-dose IL-2
No other underlying medical condition that would make the administration of the study drug hazardous or obscure the interpretation of adverse events
No other concurrent medical condition that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 3 weeks since prior immunotherapy for melanoma and recovered
No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4)
No prior high-dose (at least 600,000 IU/kg every 8 hours) interleukin-2 (IL-2)

Chemotherapy

At least 3 weeks since prior chemotherapy for melanoma and recovered
No concurrent chemotherapy

Endocrine therapy

At least 3 weeks since prior hormonal therapy for melanoma and recovered
At least 4 weeks since prior corticosteroids
No concurrent systemic or topical corticosteroids

Radiotherapy

At least 3 weeks since prior radiotherapy for melanoma and recovered

Surgery

Not specified

Other

No concurrent immunosuppressive agents (e.g., cyclosporine or its analog)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2003

Primary Completion

December 7, 2022

Study Completion (Actual)

August 1, 2006

Study Registration Dates

First Submitted

April 7, 2003

First Submitted That Met QC Criteria

April 8, 2003

First Posted (Estimate)

April 9, 2003

Study Record Updates

Last Update Posted (Estimate)

June 20, 2013

Last Update Submitted That Met QC Criteria

June 18, 2013

Last Verified

August 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

CDR0000287211
NCI-03-C-0109

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.