Interleukin-12 and Interleukin-2 in Treating Patients With Refractory or Recurrent Neuroblastoma
- Conditions
- Recurrent Neuroblastoma
- Interventions
- Biological: recombinant interleukin-12Biological: aldesleukin
- Registration Number
- NCT00054405
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 40
-
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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (IL-12, aldesleukin) recombinant interleukin-12 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. Treatment (IL-12, aldesleukin) 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.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC) 28 days
- Secondary Outcome Measures
Name Time Method Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST) Up to 3 weeks
Trial Locations
- Locations (14)
Texas Children's Hospital
🇺🇸Houston, Texas, United States
New Approaches to Neuroblastoma Treatment (NANT)
🇺🇸Los Angeles, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
University of California at San Francisco - Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
AFLAC Cancer Center and Blood Disorders Service
🇺🇸Atlanta, Georgia, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Childrens Memorial Hospital
🇺🇸Chicago, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
University of Michigan University Hospital
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States