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

February 5, 2003
April 8, 2013
December 2002
May 2009   (final data collection date for primary outcome measure)
Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00054405 on ClinicalTrials.gov Archive Site
Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Interleukin-12 and Interleukin-2 in Treating Patients With Refractory or Recurrent Neuroblastoma
A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Recurrent Neuroblastoma
  • 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
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.

Interventions:
  • Biological: recombinant interleukin-12
  • Biological: aldesleukin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
40
Not Provided
May 2009   (final data collection date for primary outcome measure)

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
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00054405
NCI-2009-00024, NANT 2001-01, CDR0000270447, P01CA081403, CDR0000270447
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Jon Wigginton New Approaches to Neuroblastoma Treatment (NANT)
National Cancer Institute (NCI)
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP