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

Recurrent Neuroblastoma Clinical Trial

Official title:

A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00054405
• Other study ID #: NCI-2009-00024
• Secondary ID: NANT 2001-01CDR0
• Status: Terminated
• Phase: Phase 1
• First received: February 5, 2003
• Last updated: April 8, 2013
• Start date: December 2002

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00065494

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma
• Recurrent Neuroblastoma

Intervention

Biological:
• recombinant interleukin-12
Given IV
• aldesleukin
Given IV

Locations

Country	Name	City	State
United States	University of Michigan University Hospital	Ann Arbor	Michigan
United States	AFLAC Cancer Center and Blood Disorders Service	Atlanta	Georgia
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Childrens Memorial Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	New Approaches to Neuroblastoma Treatment (NANT)	Los Angeles	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of California at San Francisco - Comprehensive Cancer Center	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)		28 days	Yes
Secondary	Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST)		Up to 3 weeks	No