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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Recurrent Neuroblastoma

Intervention: recombinant interleukin-12 (Biological); aldesleukin (Biological)

Phase: Phase 1

Status: Terminated

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Jon Wigginton, Principal Investigator, Affiliation: New Approaches to Neuroblastoma Treatment (NANT)


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.

Clinical Details

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

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

Primary outcome: Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)

Secondary outcome: Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST)

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.


Minimum age: 3 Years. Maximum age: 21 Years. Gender(s): Both.


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


- More than 4 weeks since prior chemotherapy

- No other unstable medical condition or critical illness that would preclude study


- 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


- 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

Locations and Contacts

Children's Hospital Los Angeles, Los Angeles, California 90027, United States

New Approaches to Neuroblastoma Treatment (NANT), Los Angeles, California 90027-6016, United States

Lucile Packard Children's Hospital Stanford University, Palo Alto, California 94304, United States

University of California at San Francisco - Comprehensive Cancer Center, San Francisco, California 94143-0875, United States

AFLAC Cancer Center and Blood Disorders Service, Atlanta, Georgia 30322, United States

Childrens Memorial Hospital, Chicago, Illinois 60614, United States

Riley Hospital for Children, Indianapolis, Indiana 46202, United States

Children's Hospital Boston, Boston, Massachusetts 02115, United States

University of Michigan University Hospital, Ann Arbor, Michigan 48109, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Texas Children's Hospital, Houston, Texas 77030, United States

Seattle Children's Hospital, Seattle, Washington 98105, United States

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States

Additional Information

Starting date: December 2002
Last updated: April 8, 2013

Page last updated: August 23, 2015

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