Interleukin-12 and Interleukin-2 in Treating Patients With Refractory or Recurrent Neuroblastoma
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
OBJECTIVES:
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Define the maximum tolerated dose and dose-limiting toxicity of interleukin-12 with or without interleukin-2 in patients with refractory or recurrent neuroblastoma.
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Determine, preliminarily, the antitumor effect of interleukin-12 with or without interleukin-2 in these patients.
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Evaluate the immunoregulatory activity of interleukin-12 with or without interleukin-2 in these patients.
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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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
Biological: aldesleukin
Given IV
Other Names:
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Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC) [28 days]
Secondary Outcome Measures
- Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [Up to 3 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of neuroblastoma
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Histologically confirmed disease AND/OR disease defined by tumor cells in the bone marrow and elevated urinary catecholamine metabolites
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Persistent and/or refractory disease, with at least 1 of the following:
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Biopsy-proven residual disease at least 12 weeks after myeloablative therapy
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Progressive disease after nonmyeloablative or myeloablative therapy
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Recurrent disease, evidenced by any of the following:
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Biopsy-proven recurrent soft tissue disease
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Metaiodobenzylguanidine (MIBG)-positive lesions visible on any other imaging modality or repeat MIBG obtained 2-4 weeks or more apart
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Histologically confirmed bone marrow disease
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Progressive or stable disease after at least 1 prior standard salvage regime
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No clinically significant pleural effusion
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ECOG 0-1
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Life expectancy >= 12 weeks
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Hepatitis A antibody negative
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Hepatitis B surface antigen negative
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Positive hepatitis B titer allowed if patient has been immunized and has no history of disease
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Hepatitis C virus negative
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No history of congenital or acquired coagulation disorder
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Cardiac function normal by ECG
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No dyspnea at rest
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No exercise intolerance
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Oxygen saturation at least 94% by pulse oximetry
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DLCO greater than 60% of predicted
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FEV1 greater than 70% of predicted
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Negative pregnancy test
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Skull-based bony lesions without space-occupying intracranial extension are allowed
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No prior or concurrent intracranial metastatic disease to the brain parenchyma
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Not pregnant or nursing
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Fertile patients must use effective barrier contraception during and for at least 2 months after study
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No prior hematologic malignancy (including leukemia or lymphoma)
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No history of malignant hyperthermia
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No prior or concurrent autoimmune disease
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No positive direct Coombs testing
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No history of ongoing or intermittent bowel obstruction
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No active infection or other significant systemic illness
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More than 2 weeks since prior fenretinide
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More than 2 weeks since prior 13-cis-retinoic acid
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More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
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More than 2 weeks since prior interferons or interleukins
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More than 2 weeks since prior cytokine-fusion proteins
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More than 2 weeks since prior IV immunoglobulin (IVIG)
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No prior interleukin-12
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No concurrent cytokines
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No concurrent fenretinide
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No concurrent 13-cis-retinoic acid
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No other concurrent immunomodulators, including:
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G-CSF and GM-CSF
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Interferons
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Other interleukins
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IVIG
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More than 4 weeks since prior chemotherapy
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No other unstable medical condition or critical illness that would preclude study participation
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More than 12 weeks since prior myeloablative chemotherapy followed by autologous stem cell transplantation:
No prior myeloablative chemotherapy followed by allogeneic bone marrow transplantation
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More than 2 weeks since prior growth hormones
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More than 4 weeks since prior systemic corticosteroids
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More than 2 weeks since prior non-corticosteroid hormonal therapy (including oral birth control pills)
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No concurrent hormonal therapy (including oral birth control pills)
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No concurrent growth hormones
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No concurrent systemic corticosteroids, except for use in life-threatening complications
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More than 4 weeks since prior radiotherapy
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No prior solid organ transplantation
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More than 4 weeks since prior investigational agents
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No other concurrent investigational agents
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No prior enrollment on COG-A3973, unless disease has progressed
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No history of hemolytic anemia
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Absolute neutrophil count at least 1,500/mm^3 [Note: Independent of growth factor or transfusion support]
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Platelet count at least 75,000/mm^3 [Note: Independent of growth factor or transfusion support]
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AST and ALT less than 2.5 times upper limit of normal
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Bilirubin less than 2.0 mg/dL
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Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR creatinine normal
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HIV negative
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Ejection fraction at least 50% by echocardiogram or MUGA OR Fractional shortening at least 30% by echocardiogram
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No congestive heart failure
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No uncontrolled cardiac arrhythmia
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | New Approaches to Neuroblastoma Treatment (NANT) | Los Angeles | California | United States | 90027-6016 |
2 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
3 | Lucile Packard Children's Hospital Stanford University | Palo Alto | California | United States | 94304 |
4 | University of California at San Francisco - Comprehensive Cancer Center | San Francisco | California | United States | 94143-0875 |
5 | AFLAC Cancer Center and Blood Disorders Service | Atlanta | Georgia | United States | 30322 |
6 | Childrens Memorial Hospital | Chicago | Illinois | United States | 60614 |
7 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
8 | Children's Hospital Boston | Boston | Massachusetts | United States | 02115 |
9 | University of Michigan University Hospital | Ann Arbor | Michigan | United States | 48109 |
10 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
11 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
12 | Texas Children's Hospital | Houston | Texas | United States | 77030 |
13 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
14 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Jon Wigginton, New Approaches to Neuroblastoma Treatment (NANT)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00024
- NANT 2001-01
- CDR0000270447
- P01CA081403
- CDR0000270447
- NCT00065494