Interleukin-12 Followed by Interferon Alfa in Treating Patients With Advanced Cancer

NCT ID: NCT00003451

Last Updated: 2013-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-08-31

Brief Summary

Phase I trial to study the effectiveness of combining interleukin-12 and interferon alfa in treating patients who have residual, recurrent, or metastatic malignant melanoma or other advanced cancer that has not responded to standard therapy. Interleukin-12 may stimulate a person's white blood cells to kill cancer cells. Interferon alfa may interfere with the growth of the cancer cells. Combining interleukin-12 with interferon alfa may kill more cancer cells.

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of interferon alfa when preceded by a single dose of interleukin-12 in patients with recurrent or metastatic melanoma or other advanced malignancies.

OUTLINE: This is a dose-escalation study.

Cohorts of 3 patients receive interleukin-12 IV push on day 1, followed by escalating doses of interferon alfa by subcutaneous injection at 24, 48, 72, 96 and 120 hours. Courses repeat every 2 weeks for 6 months (12 courses total) in the absence of unacceptable toxicity and disease progression. Patients achieving partial response or stable disease at the completion of 6 months of therapy may receive additional courses of therapy for up to 24 months. Dose escalation of interferon alfa continues in subsequent cohorts in the absence of dose limiting toxicity (DLT). If 1 of 3 patients experiences DLT at a dose level, then 3 additional patients are entered at that dose level. If 2 of 6 patients experience DLT, then dose escalation stops. The maximum tolerated dose is defined as 1 level below that dose at which 2 or more of 6 patients experience DLT. Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Cohorts of 3 patients receive interleukin-12 IV push on day 1, followed by escalating doses of interferon alfa by subcutaneous injection at 24, 48, 72, 96 and 120 hours. Courses repeat every 2 weeks for 6 months (12 courses total) in the absence of unacceptable toxicity and disease progression. Patients achieving partial response or stable disease at the completion of 6 months of therapy may receive additional courses of therapy for up to 24 months. Dose escalation of interferon alfa continues in subsequent cohorts in the absence of dose limiting toxicity (DLT). If 1 of 3 patients experiences DLT at a dose level, then 3 additional patients are entered at that dose level. If 2 of 6 patients experience DLT, then dose escalation stops. The maximum tolerated dose is defined as 1 level below that dose at which 2 or more of 6 patients experience DLT. Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Group Type: EXPERIMENTAL

recombinant interferon alfa

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Interventions

recombinant interferon alfa

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed residual, recurrent, or metastatic malignant melanoma or other advanced malignancies
• Must have failed standard curative and/or palliative therapies
• No brain or central nervous system metastases

PATIENT CHARACTERISTICS:

• Age: 13 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: At least 12 weeks
• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL (may be posttransfusion or may receive erythropoietin)
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2 times ULN
• Creatinine no greater than 1.5 times ULN
• Creatinine clearance at least 60 mL/min
• Calcium no greater than 11 mg/dL (may receive agents to decrease calcium)
• No significant cardiovascular disease
• No cardiac arrhythmia requiring drug or device intervention
• No history of significant peripheral neuropathy
• No significant central nervous system disease
• HIV negative Hepatitis B surface antigen negative
• No concurrent serious infection requiring intravenous antibiotic therapy
• No clinically significant autoimmune disease (i.e., rheumatoid arthritis)
• No clinically significant gastrointestinal bleeding or uncontrolled peptic ulcer disease
• No history of inflammatory bowel disease
• No other major illness that substantially increases the risk associated with participation in this study
• Not pregnant or nursing Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior biologic therapy
• At least 4 weeks since prior chemotherapy
• No concurrent systemic corticosteroids
• At least 2 weeks since prior local radiotherapy
• At least 2 weeks since surgery Other: At least 4 weeks since prior investigational drug

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William E. Carson, MD

Role: STUDY_CHAIR

Ohio State University Comprehensive Cancer Center

Locations

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Countries

United States

Other Identifiers

OSU-T98-0020

Identifier Type: -

Identifier Source: secondary_id

NCI-T98-0020

Identifier Type: -

Identifier Source: secondary_id

CDR0000066482

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01397

Identifier Type: -

Identifier Source: org_study_id