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Phase III Randomized Study of Adjuvant Isotretinoin With or Without Monoclonal Antibody Ch14.18, Interleukin-2, and Sargramostim (GM-CSF) in Patients With Neuroblastoma Who Have Completed Myeloablative Therapy and Autologous Stem Cell Transplantation (Arm I Closed to Accrual as of 4/16/2009)
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Related Information Registry Information
Alternate Title
Isotretinoin With or Without Monoclonal Antibody, Interleukin-2, and Sargramostim Following Stem Cell Transplantation in Treating Patients With Neuroblastoma
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase III | Treatment | Active | 30 and under at diagnosis | COG-ANBL0032 ANBL0032, COG-P9842, NCT00026312 |
Objectives Primary - Compare the event-free survival of patients with neuroblastoma who have completed myeloablative therapy and autologous stem cell transplantation (ASCT) when treated with adjuvant isotretinoin with or without monoclonal antibody Ch14.18, interleukin-2, and sargramostim (GM-CSF).
Secondary - Compare the overall survival of patients treated with these regimens.
- Compare the event-free survival of the subgroup of high-risk, stage IV patients treated with these regimens.
- Compare the reduction of minimal residual disease (MRD) in patients treated with these regimens.
- Determine whether change from baseline MRD is associated with event-free and overall survival in patients treated with these regimens.
- Determine whether tumor biology at diagnosis correlates with event-free and overall survival in patients treated with these regimens.
- Determine the toxic effects of this combination regimen in these patients.
- Determine whether antibody-dependent cellular cytotoxicity correlates with event-free survival in patients treated with these regimens.
- Determine the descriptive profile of human anti-chimeric antibody (HACA) during immunotherapy.
- Compare outcome data of patients with persistent disease with historical data after being treated with these regimens.
- Correlate the pharmacokinetics and pharmacogenomic parameters with event-free survival
or systemic toxicity.
- Further describe and refine the event-free survival and overall survival estimates and baseline characteristics for patients
treated with isotretinoin, monoclonal antibody Ch14.18, and interleukin-2 following cessation of the randomized portion of the study.
- Further describe the safety and toxicity of isotretinoin, monoclonal antibody Ch14.18, and interleukin-2 in these patients following cessation of the randomized portion of the study including the
number of courses delivered per patient, the number of dose reductions or stoppage (CH14.18 and/or interleukin-2) and the number of toxic deaths.
Entry Criteria Disease Characteristics:
- Diagnosis of neuroblastoma
- Categorized as high risk at diagnosis
- Meets all of the following criteria:
- Patients much have completed therapy including intensive induction followed by autologous stem cell transplantation (ASCT) and radiotherapy
- Completed frontline therapies, examples of such therapy includes:
- Following treatment per COG-A3973 protocol
- Following treatment per POG-9340-42
- Following treatment per CCG-3891
- Following treatment on NANT-2001-02
- Enrollment on or following treatment per COG-ANBL02P1 protocol
- Enrollment on or following treatment per ANBL07P1
- Tandem transplant patients are eligible
- Following enrollment and treatment on or per COG-ANBL0532
- Following treatment per POG-9640 protocol
- Following treatment per COG-ANBL00P1 protocol
- Following treatment per CHP 594 or DFCI 34-DAT
- Other frontline therapy with permission from study chairs
- Patients with biopsy confirmed residual disease after ASCT are eligible
- Must meet the International Neuroblastoma Response Criteria (INRC)
for CR, VGPR, or PR for primary site, soft tissue metastases, and bone metastases AND must also meet the protocol specified criteria for bone marrow response as follows:
- No more than 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone
marrow aspirate/biopsy
- Patient who have no tumor seen on the prior bone marrow, and then have ≤ 10% tumor on any of
the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment
evaluation will also be eligible
- No more than 9 months from starting the first induction chemotherapy after diagnosis to the date of ASCT *
- No progressive disease at time of registration except for protocol specified bone marrow response
[Note: * For tandem ASCT patients this is the date of the first stem cell infusion] Prior/Concurrent Therapy:
Biologic therapy: - See Disease Characteristics
- No more than 1 prior stem cell transplantation
- No other concurrent cytokines or growth factors (e.g.,
filgrastim [G-CSF] or interferon)
- No IV immunoglobulin G within 2 weeks before, during, and for
1 week after monoclonal antibody Ch14.18 (arm II patients)
- No prior anti-GD2 antibody therapy
Chemotherapy: - No more than 1 prior myeloablative consolidation regimen
- No concurrent myelosuppressive chemotherapy (arm II
patients)
Endocrine therapy: - No concurrent corticosteroids unless for life-threatening
conditions (e.g., increased intracranial pressure from CNS tumors or
life-threatening allergic reactions)
Radiotherapy: - See Disease Characteristics
- At least 7 days since prior radiotherapy
Surgery: Other: - No other concurrent anticancer therapy
- No concurrent immunosuppressive drugs (e.g.,
cyclosporine)
- No concurrent pentoxifylline
- No radiographic contrast materials during and for at least 1
week after interleukin-2 (arm II)
Patient Characteristics:
Age: - 30 and under at diagnosis
Performance status: - Lansky 50-100%
OR - Karnofsky 50-100%
Life expectancy: Hematopoietic: - Total absolute phagocyte count (neutrophils and monocytes) ≥ 1,000/mm3
Hepatic: - Bilirubin ≤ 1.5 times normal
- SGPT ≤ 5 times normal
- Veno-occlusive disease (if present) stable or improving
Renal: - Creatinine adjusted according to age as follows:
- No greater than 0.4 mg/dL (≤ 5 months)
- No greater than 0.5 mg/dL (6 months -11 months)
- No greater than 0.6 mg/dL (1 year-23 months)
- No greater than 0.8 mg/dL (2 years-5 years)
- No greater than 1.0 mg/dL (6 years-9 years)
- No greater than 1.2 mg/dL (10 years-12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 years to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male])
OR - Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
Cardiovascular: - Shortening fraction ≥ 30% by echocardiogram
OR - Ejection fraction ≥ 55% by MUGA
Pulmonary: - FEV1 and FVC > 60% predicted by pulmonary function
test
OR - No evidence of dyspnea at rest, no exercise intolerance
Other: - Not pregnant
- Fertile patients must use effective contraception
- Seizure disorder allowed if well-controlled and on
anticonvulsants
- CNS toxicity < grade 2
Expected Enrollment 423A total of 423 patients will be accrued for this study within 5 years. Outcomes Primary Outcome(s)Event-free survival (EFS)
Secondary Outcome(s)Overall survival (OS) Reduction of minimal residual disease (MRD) Association between change from baseline MRD and EFS and OS Correlation of tumor biology at diagnosis with EFS and OS Toxic effects Correlation of antibody-dependent cellular cytotoxicity with event-free survival Comparison of outcome of patients with persistent disease with historical data Correlation of pharmacokinetic and pharmacogenomic parameters with EFS or systemic toxicity
Outline This is a randomized, multicenter study. Patients are stratified
according to pre-autologous stem cell transplantation (ASCT) response
(complete vs very good partial vs partial), stem cells received (purged vs
unpurged), and frontline chemotherapy (COG-A3973 vs POG 9341/9342 vs COG-ANGL02P1 vs other therapy). A further stratum consists of patients with biopsy-confirmed post-ASCT
persistent disease who are also enrolled on COG-A3973 or COG-ANBL0532. These patients are not randomized but assigned to
treatment arm II. Patients in the first set of strata are randomized to 1 of 2 treatment
arms. - Arm I (closed to accrual as of 4/16/2009): Beginning on day 67 post-ASCT, patients receive oral
isotretinoin twice daily for 14 days. Treatment repeats every 28 days for 6
courses in the absence of disease progression or unacceptable toxicity. Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy.
- Arm II: Beginning on day 56 post-ASCT, patients receive immunotherapy
comprising sargramostim (GM-CSF) subcutaneously (SC) or IV over 2 hours on
days 0-13 during courses 1, 3, and 5 and monoclonal antibody Ch14.18 IV over 10-20
hours on days 3-6 of courses 1-5. Patients also receive interleukin-2 IV
continuously on days 0-3 and 7-10 during courses 2 and 4. Immunotherapy
repeats every 28 days for 5 courses in the absence of disease progression or
unacceptable toxicity. Patients also receive oral isotretinoin as in arm I
beginning on day 11 of immunotherapy.
Patients are followed periodically for 10 years.
Trial Contact Information
Trial Lead Organizations Children's Oncology Group | | | Alice Yu, MD, PhD, Protocol chair | | | | Trial Sites
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U.S.A. |
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Kentucky |
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Louisville |
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| | | | | | | | Kosair Children's Hospital |
| | Clinical Trials Office - Kosair Children's Hospital | |
| Email:
CancerResource@nortonhealthcare.org |
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Louisiana |
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New Orleans |
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| | | Children's Hospital of New Orleans |
| | Clinical Trials Office - Children's Hospital of New Orleans | |
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Minnesota |
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Minneapolis |
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| | | Masonic Cancer Center at University of Minnesota |
| | Clinical Trials Office - Masonic Cancer Center at University of Minnesota | |
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New York |
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Valhalla |
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| | | New York Medical College |
| | Fevzi Ozkaynak | |
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Ohio |
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Cleveland |
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| | | Cleveland Clinic Taussig Cancer Center |
| | Clinical Trials Office - Cleveland Clinic Taussig Cancer Center | |
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Dayton |
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| | Children's Medical Center - Dayton |
| | Emmett Broxson | |
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Pennsylvania |
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Philadelphia |
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| | | Children's Hospital of Philadelphia |
| | Richard Aplenc | |
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South Carolina |
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Columbia |
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| | | Palmetto Health South Carolina Cancer Center |
| | Clinical Trials Office - Palmetto Health South Carolina Cancer Center | |
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Washington |
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Seattle |
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| | | Children's Hospital and Regional Medical Center - Seattle |
| | Julie Park | |
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Spokane |
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| | Providence Cancer Center at Sacred Heart Medical Center |
| | Judy Felgenhauer | |
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Related Information PDQ® clinical trial COG-A3973 PDQ® clinical trial COG-ANBL02P1 PDQ® clinical trial CCG-3891 PDQ® clinical trial NANT-2001-02 PDQ® clinical trial COG-ANBL0532 PDQ® clinical trial POG-9340-42
Registry Information | | Official Title | | Phase III Randomized Study Of Chimeric Antibody 14.18 (CH14.18) In High Risk Neuroblastoma Following Myeloablative Therapy And Autologous Stem Cell Rescue | | Trial Start Date | | 2001-10-18 | | Trial Completion Date | | 2012-06-01 (estimated) | | Registered in ClinicalTrials.gov | | NCT00026312 | | Date Submitted to PDQ | | 2001-09-14 | | Information Last Verified | | 2009-05-13 | | NCI Grant/Contract Number | | CA30969 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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