search
Back to results

3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow

Primary Purpose

Neuroblastoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic
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), 09-161

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 or MYCN-amplified stage 4S.
  • Patients have primary refractory disease limited to BM, i.e., high-risk NB (defined above) resistant to standard therapy, as evidenced by incomplete response in BM, but no measurable MIBG-avid soft tissue tumor assessable for response and no progressive disease.
  • 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 v 4.0) 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

Arm Description

This phase II study of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response in of primary refractory neuroblastoma in bone marrow (i.e., incomplete response to standard treatment).

Outcomes

Primary Outcome Measures

Assess the Activity of High-dose 3F8/GM-CSF
against persistent neuroblastoma in bone marrow of patients who have no other evidence of disease by standard studies.

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 progression-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
July 24, 2019
Sponsor
Memorial Sloan Kettering Cancer Center
search

1. Study Identification

Unique Protocol Identification Number
NCT01183897
Brief Title
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow
Official Title
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow: A Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
August 12, 2010 (Actual)
Primary Completion Date
September 25, 2018 (Actual)
Study Completion Date
September 25, 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 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), 09-161

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic
Arm Type
Experimental
Arm Description
This phase II study of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response in of primary refractory neuroblastoma in bone marrow (i.e., incomplete response to standard treatment).
Intervention Type
Biological
Intervention Name(s)
3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic
Intervention 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 (20mg/m2/day) for all cycles The patients have primary refractory BM disease. Protocol treatment is through 24 months. Real-time quantitative RT-PCR63-65 will be used to assess MRD in BM. 13-cis-retinoic acid is started no later than after cycle 4 (i.e., after response is scored), but sooner if CR is achieved after cycles 1, 2, or 3, or if early HAMA develops.
Primary Outcome Measure Information:
Title
Assess the Activity of High-dose 3F8/GM-CSF
Description
against persistent neuroblastoma in bone marrow of patients who have no other evidence of disease by standard studies.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Apply Real-time Quantitative RT-PCR
Description
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 progression-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 or MYCN-amplified stage 4S. Patients have primary refractory disease limited to BM, i.e., high-risk NB (defined above) resistant to standard therapy, as evidenced by incomplete response in BM, but no measurable MIBG-avid soft tissue tumor assessable for response and no progressive disease. 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 v 4.0) 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 Primary Refractory Neuroblastoma in Bone Marrow

We'll reach out to this number within 24 hrs