Back to results3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma
Primary Purpose
Neuroblastoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring GM-CSF, MAB 3F8, RETINOIC ACID (CIS-9 & 13), 09-160
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.
- High-risk NB as defined by risk-related treatment guidelines1 and the International NB Staging System,89 i.e., stage 4 with (any age) or without (> or = to 18 months of age) MYCN amplification, MYCN-amplified stage 2 or stage 3 (any age), or MYCN-amplified stage 4S.
- The patients are in >2nd CR/VGPR, including no measurable MIBG-avid soft tissue tumor assessable for response.
- Signed informed consent indicating awareness of the investigational nature of this program.
Exclusion Criteria:
- Creatinine > 3.0 mg/dL
- ALT, AST and Alkaline Phosphatase > 5.0 times the upper limit of normal
- Bilirubin > 3.0 mg/dL
- Patients with grade 3 or higher toxicities (using the CTCAE v34.0) related to cardiac, neurological, pulmonary or gastrointestinal function as determined by physical exam. Patients must have normal blood pressure for age.
- Progressive disease
- History of allergy to mouse proteins
- Active life-threatening infection.
- Human anti-mouse antibody (HAMA) titer >1000 Elisa units/ml.
- Inability to comply with protocol requirements.
Sites / Locations
- Memorial Sloan-Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid
Arm Description
This phase II, open-label, single arm trial assesses the anti-NB activity of high-dose 3F8 (80 mg/m2/day), which is used in cycles 1-2, with return to standard 3F8 dosage (20 mg/m2/day) in subsequent cycles. Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. Starting with A(6), patients no longer receive high-dose 3F8 but receive only standard dose 3F8 (20 mg/m2/day) for all cycles.
Outcomes
Primary Outcome Measures
Assess the Impact of High-dose 3F8/GM-CSF on Relapse-free Survival
in patients in second or greater complete or very good partial remission, but at high risk of additional relapse.
Secondary Outcome Measures
Apply Real-time Quantitative RT-PCR to Test the Hypothesis That the Minimal Residual Disease Content of Bone Marrow
after the first treatments with 3F8/GMCSF has significant prognostic impact on relapse-free survival.
Monitor Safety of the High-dose Antibody Treatment
to assure no side-effects or noxious sequelae develop or emerge that were not seen in the prior phase I study.
Full Information
NCT ID
NCT01183884
First Posted
August 16, 2010
Last Updated
November 12, 2019
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT01183884
Brief Title
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma
Official Title
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma: A Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Terminated
Why Stopped
Low participant accrual
Study Start Date
August 2010 (undefined)
Primary Completion Date
November 9, 2018 (Actual)
Study Completion Date
November 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to find out what effects, good and/or bad, the combination of 3F8 and GM-CSF has on the patient and the cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
GM-CSF, MAB 3F8, RETINOIC ACID (CIS-9 & 13), 09-160
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid
Arm Type
Experimental
Arm Description
This phase II, open-label, single arm trial assesses the anti-NB activity of high-dose 3F8 (80 mg/m2/day), which is used in cycles 1-2, with return to standard 3F8 dosage (20 mg/m2/day) in subsequent cycles. Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. Starting with A(6), patients no longer receive high-dose 3F8 but receive only standard dose 3F8 (20 mg/m2/day) for all cycles.
Intervention Type
Biological
Intervention Name(s)
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid
Intervention Description
3F8 (80 mg/m2/day), which is used in cycles 1-2, with return to standard 3F8 dosage (20 mg/m2/day) in subsequent cycles .Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage.
Starting with A(6), patients no longer receive high-dose 3F8 but receive only standard dose 3F8 (20 mg/m2/day) for all cycles. The patients are in > or = to 2nd CR/VGPR and at high risk for additional relapse. Real-time quantitative RT-PCR63-65 will be used to assess MRD in BM. 13-cis-retinoic acid is started after cycle 2.
Primary Outcome Measure Information:
Title
Assess the Impact of High-dose 3F8/GM-CSF on Relapse-free Survival
Description
in patients in second or greater complete or very good partial remission, but at high risk of additional relapse.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Apply Real-time Quantitative RT-PCR to Test the Hypothesis That the Minimal Residual Disease Content of Bone Marrow
Description
after the first treatments with 3F8/GMCSF has significant prognostic impact on relapse-free survival.
Time Frame
2 years
Title
Monitor Safety of the High-dose Antibody Treatment
Description
to assure no side-effects or noxious sequelae develop or emerge that were not seen in the prior phase I study.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.
High-risk NB as defined by risk-related treatment guidelines1 and the International NB Staging System,89 i.e., stage 4 with (any age) or without (> or = to 18 months of age) MYCN amplification, MYCN-amplified stage 2 or stage 3 (any age), or MYCN-amplified stage 4S.
The patients are in >2nd CR/VGPR, including no measurable MIBG-avid soft tissue tumor assessable for response.
Signed informed consent indicating awareness of the investigational nature of this program.
Exclusion Criteria:
Creatinine > 3.0 mg/dL
ALT, AST and Alkaline Phosphatase > 5.0 times the upper limit of normal
Bilirubin > 3.0 mg/dL
Patients with grade 3 or higher toxicities (using the CTCAE v34.0) related to cardiac, neurological, pulmonary or gastrointestinal function as determined by physical exam. Patients must have normal blood pressure for age.
Progressive disease
History of allergy to mouse proteins
Active life-threatening infection.
Human anti-mouse antibody (HAMA) titer >1000 Elisa units/ml.
Inability to comply with protocol requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian Kushner, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23633099
Citation
Kushner BH, Modak S, Basu EM, Roberts SS, Kramer K, Cheung NK. Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD2 3F8 monoclonal antibody. Cancer. 2013 Aug 1;119(15):2789-95. doi: 10.1002/cncr.28137. Epub 2013 Apr 30.
Results Reference
derived
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan-Kettering Cancer Center
Learn more about this trial
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma
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