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High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Myeloablative Therapy and Autologous Stem-Cell Transplantation

Primary Purpose

Neuroblastoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
3F8 monoclonal antibody and 13-cis-Retinoic Acid
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring GM-CSF, MAB 3F8, RETINOIC ACID (CIS-9 & 13), 09-158

Eligibility Criteria

18 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 post-stem cell transplantation and in first 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 v3.0) 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 monoclonal antibody and 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. The patients are post-transplant and in 1st complete/very good partial remission (CR/VGPR),89 with no evidence of NB by standard studies, but are at high risk for relapse.

Outcomes

Primary Outcome Measures

Assess the Impact of High-dose 3F8/GM-CSF on Relapse-free Survival
in patients who are post-stem-cell transplantation and in first complete or very good partial remission, but at high risk of 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

First Posted
August 16, 2010
Last Updated
September 16, 2019
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01183416
Brief Title
High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Myeloablative Therapy and Autologous Stem-Cell Transplantation
Official Title
High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Myeloablative Therapy and Autologous Stem-Cell Transplantation in Patients With High-Risk Neuroblastoma: A Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
October 31, 2018 (Actual)
Study Completion Date
October 31, 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 see if high-dose 3F8 combined with GM-CSF is better than standard dose 3F8 in treating neuroblastoma. Another purpose of the study is to find out what effects, good and/or bad, 3F8 has on cancer. The investigators also want to see if the antibody works against a very small amount of neuroblastoma (minimal residual disease) that is left in the bone marrow.

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), 09-158

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
3F8 monoclonal antibody and 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. The patients are post-transplant and in 1st complete/very good partial remission (CR/VGPR),89 with no evidence of NB by standard studies, but are at high risk for relapse.
Intervention Type
Drug
Intervention Name(s)
3F8 monoclonal antibody and 13-cis-Retinoic Acid
Intervention Description
A cycle consists of treatment with 3F8 for 5 days. GMCSF is started 5 days in advance of each 3F8 cycle. The break between end of a cycle of 3F8/GM-CSF and start of next cycle is 2-to-4-weeks through 4 cycles; subsequent breaks are ~6-8 weeks. 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 who are post-stem-cell transplantation and in first complete or very good partial remission, but at high risk of 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 post-stem cell transplantation and in first 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 v3.0) 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

High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Myeloablative Therapy and Autologous Stem-Cell Transplantation

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