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

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00054405
First received: February 5, 2003
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Neuroblastoma
Biological: recombinant interleukin-12
Biological: aldesleukin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: December 2002
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Biological: recombinant interleukin-12
Given IV
Other Names:
  • cytotoxic lymphocyte maturation factor
  • IL-12
  • interleukin-12
  • natural killer cell stimulatory factor
  • Ro 24-7472
Biological: aldesleukin
Given IV
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00054405

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
New Approaches to Neuroblastoma Treatment (NANT)
Los Angeles, California, United States, 90027-6016
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
University of California at San Francisco - Comprehensive Cancer Center
San Francisco, California, United States, 94143-0875
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service
Atlanta, Georgia, United States, 30322
United States, Illinois
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Jon Wigginton New Approaches to Neuroblastoma Treatment (NANT)
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00054405     History of Changes
Obsolete Identifiers: NCT00065494
Other Study ID Numbers: NCI-2009-00024, NANT 2001-01, CDR0000270447, P01CA081403, CDR0000270447
Study First Received: February 5, 2003
Last Updated: April 8, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aldesleukin
Interleukin-2
Interleukin-12
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Adjuvants, Immunologic
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on August 19, 2014