Interleukin-12 and Interleukin-2 in Treating Patients With Refractory or Recurrent Neuroblastoma

NCT ID: NCT00054405

Last Updated: 2013-04-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-12-31

Brief Summary

Phase I trial to compare the effectiveness of interleukin-12 with or without interleukin-2 in treating young patients who have refractory or recurrent neuroblastoma. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining interleukin-2 with interleukin-12 may kill more tumor cells.

Detailed Description

OBJECTIVES:

I. Define the maximum tolerated dose and dose-limiting toxicity of interleukin-12 with or without interleukin-2 in patients with refractory or recurrent neuroblastoma.

II. Determine, preliminarily, the antitumor effect of interleukin-12 with or without interleukin-2 in these patients.

III. Evaluate the immunoregulatory activity of interleukin-12 with or without interleukin-2 in these patients.

IV. Evaluate the antiangiogenic activity of interleukin-12 with or without interleukin-2 in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 2 treatment cohorts.

COHORT A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8, 10, and 12.

COHORT B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and 8 and IL-12 IV as in cohort A.

Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may receive additional courses at the discretion of the principal investigator.

Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 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.

Once the MTD is determined, an additional cohort of 8 patients receives IL-12 and IL-2 at the MTD.

Patients are followed at 3 weeks.

Conditions

Recurrent Neuroblastoma

Study Design

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

Study Groups

Treatment (IL-12, aldesleukin)

Cohort A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8, 10, and 12.

Cohort B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and 8 and IL-12 IV as in cohort A.

Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may receive additional courses at the discretion of the principal investigator.

Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 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.

Once the MTD is determined, an additional cohort of 8 patients receives IL-12 and IL-2 at the MTD.

Group Type: EXPERIMENTAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Given IV

aldesleukin

Intervention Type: BIOLOGICAL

Given IV

Interventions

recombinant interleukin-12

Given IV

Intervention Type: BIOLOGICAL

aldesleukin

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

cytotoxic lymphocyte maturation factor; IL-12; interleukin-12; natural killer cell stimulatory factor; Ro 24-7472; IL-2; Proleukin; recombinant human interleukin-2; recombinant interleukin-2

Eligibility Criteria

Inclusion Criteria

• Diagnosis of neuroblastoma

• Histologically confirmed disease AND/OR disease defined by tumor cells in the bone marrow and elevated urinary catecholamine metabolites
• Persistent and/or refractory disease, with at least 1 of the following:

• Biopsy-proven residual disease at least 12 weeks after myeloablative therapy
• Progressive disease after nonmyeloablative or myeloablative therapy
• Recurrent disease, evidenced by any of the following:

• Biopsy-proven recurrent soft tissue disease
• Metaiodobenzylguanidine (MIBG)-positive lesions visible on any other imaging modality or repeat MIBG obtained 2-4 weeks or more apart
• Histologically confirmed bone marrow disease
• Progressive or stable disease after at least 1 prior standard salvage regime
• No clinically significant pleural effusion
• ECOG 0-1
• Life expectancy >= 12 weeks
• Hepatitis A antibody negative
• Hepatitis B surface antigen negative

• Positive hepatitis B titer allowed if patient has been immunized and has no history of disease
• Hepatitis C virus negative
• No history of congenital or acquired coagulation disorder
• Cardiac function normal by ECG
• No dyspnea at rest
• No exercise intolerance
• Oxygen saturation at least 94% by pulse oximetry
• DLCO greater than 60% of predicted
• FEV1 greater than 70% of predicted
• Negative pregnancy test
• Skull-based bony lesions without space-occupying intracranial extension are allowed
• No prior or concurrent intracranial metastatic disease to the brain parenchyma
• Not pregnant or nursing
• Fertile patients must use effective barrier contraception during and for at least 2 months after study
• No prior hematologic malignancy (including leukemia or lymphoma)
• No history of malignant hyperthermia
• No prior or concurrent autoimmune disease
• No positive direct Coombs testing
• No history of ongoing or intermittent bowel obstruction
• No active infection or other significant systemic illness
• More than 2 weeks since prior fenretinide
• More than 2 weeks since prior 13-cis-retinoic acid
• More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• More than 2 weeks since prior interferons or interleukins
• More than 2 weeks since prior cytokine-fusion proteins
• More than 2 weeks since prior IV immunoglobulin (IVIG)
• No prior interleukin-12
• No concurrent cytokines
• No concurrent fenretinide
• No concurrent 13-cis-retinoic acid
• No other concurrent immunomodulators, including:

• G-CSF and GM-CSF
• Interferons
• Other interleukins
• IVIG
• More than 4 weeks since prior chemotherapy
• No other unstable medical condition or critical illness that would preclude study participation
• More than 12 weeks since prior myeloablative chemotherapy followed by autologous stem cell transplantation:

No prior myeloablative chemotherapy followed by allogeneic bone marrow transplantation

• More than 2 weeks since prior growth hormones
• More than 4 weeks since prior systemic corticosteroids
• More than 2 weeks since prior non-corticosteroid hormonal therapy (including oral birth control pills)
• No concurrent hormonal therapy (including oral birth control pills)
• No concurrent growth hormones
• No concurrent systemic corticosteroids, except for use in life-threatening complications
• More than 4 weeks since prior radiotherapy
• No prior solid organ transplantation
• More than 4 weeks since prior investigational agents
• No other concurrent investigational agents
• No prior enrollment on COG-A3973, unless disease has progressed
• No history of hemolytic anemia
• Absolute neutrophil count at least 1,500/mm^3 [Note: Independent of growth factor or transfusion support]
• Platelet count at least 75,000/mm^3 [Note: Independent of growth factor or transfusion support]
• AST and ALT less than 2.5 times upper limit of normal
• Bilirubin less than 2.0 mg/dL
• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR creatinine normal
• HIV negative
• Ejection fraction at least 50% by echocardiogram or MUGA OR Fractional shortening at least 30% by echocardiogram
• No congestive heart failure
• No uncontrolled cardiac arrhythmia

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jon Wigginton

Role: PRINCIPAL_INVESTIGATOR

New Approaches to Neuroblastoma Treatment (NANT)

Locations

New Approaches to Neuroblastoma Treatment (NANT)

Los Angeles, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

University of California at San Francisco - Comprehensive Cancer Center

San Francisco, California, United States

AFLAC Cancer Center and Blood Disorders Service

Atlanta, Georgia, United States

Childrens Memorial Hospital

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Children's Hospital Boston

Boston, Massachusetts, United States

University of Michigan University Hospital

Ann Arbor, Michigan, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Texas Children's Hospital

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

NANT 2001-01

Identifier Type: -

Identifier Source: secondary_id

CDR0000270447

Identifier Type: -

Identifier Source: secondary_id

P01CA081403

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000270447

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2009-00024

Identifier Type: -

Identifier Source: org_study_id

NCT00065494

Identifier Type: -

Identifier Source: nct_alias