Anti-GD2 3F8 Monoclonal Antibody and GM-CSF for High-Risk Neuroblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02100930
First received: March 27, 2014
Last updated: NA
Last verified: March 2014
History: No changes posted
  Purpose

The purpose of this study is to be able to supply an experimental combination of drugs called 3F8 and GM-CSF (also called sargramostim) to patients with high-risk neuroblastoma who may benefit from treatment.


Condition Intervention
Neuroblastoma
Biological: Anti-GD2 3F8 Monoclonal Antibody
Drug: GM-CSF (granulocyte-macrophage colony-stimulating factor)
Drug: oral isotretinoin

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anti-GD2 3F8 Monoclonal Antibody and GM-CSF for High-Risk Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • relapse-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    for patients treated in CR/VGPR -Disease status is defined by the International Neuroblastoma Response Criteria,supplemented by results of MIBG (metaiodobenzylguanidine) scans

  • complete remission [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    of BM disease for patients with primary refractory NB- Disease status is defined by the International Neuroblastoma Response Criteria,supplemented by results of MIBG (metaiodobenzylguanidine) scans


Estimated Enrollment: 125
Study Start Date: March 2014
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neuroblastoma
This is a single-arm, open label, open access study to provide the anti-GD2 murine IgG3 MoAb 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with high-risk neuroblastoma (NB). This immunotherapy has shown efficacy against minimal residual disease (MRD) in such patients.
Biological: Anti-GD2 3F8 Monoclonal Antibody Drug: GM-CSF (granulocyte-macrophage colony-stimulating factor) Drug: oral isotretinoin

Detailed Description:

This treatment uses 3F8/GM-CSF and isotretinoin for: Group 1 patients are in 1st CR/VGPR; Group 2 patients are in a ≥2nd CR/VGPR; and Group 3 patients have primary refractory NB in BM. All patients will receive 3F8/GM-CSF through 24 months.

Road Map/Schema for Group 1 (1st CR/VGPR) and Group 2 (≥2nd CR/VGPR) patients:

Cycle 1 3F8 (iv) + GM-CSF subcutaneous (sc) (1 wk) 2-4-wk interval Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8. * assessment of BM status by standard histology

Road Map/Schema for Group 3 patients (BM positive): The break between end of a cycle of 3F8/GM-CSF and start of next cycle is approximately 2-to-4-weeks through 4 cycles after achievement of CR in BM; subsequent breaks are ~6-8 weeks. Please see roadmap below for a patient achieving CR in BM after cycle 1. Cycle 1 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval* - BM negative Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8.

* assessment of BM response by standard histology

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of NB as defined by international criteria,62 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels.
  • High-risk NB, as defined by risk-related treatment guidelines and the International NB Staging System, i.e., stage 4 with (any age) or without (>18 months) MYCNamplification, 63 or MYCN-amplified NB other than stage 1.64,65
  • Patients are in CR/VGPR or have primary refractory NB in BM - i.e., NB resistant to standard therapy, as evidenced by persistence of NB in BM by histology or MIBG scan, but all other findings in scans show VGPR.
  • Children and adults are eligible.
  • Signed informed consent indicating awareness of the scheduling and side effects, as well as testing requirements, of this program.

Exclusion Criteria:

  • Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity > or = to grade 3, except for grade 3 hematologic toxicity.
  • Progressive disease (PD)
  • History of allergy to mouse proteins.
  • Active life-threatening infection.
  • Human anti-mouse antibody (HAMA) titer >1000 Elisa units/ml.
  • Pregnant women
  • Inability to comply with protocol requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02100930

Contacts
Contact: Brian Kushner, MD 212-639-6793
Contact: Nai-Kong Cheung, MD, PhD 646-888-2313

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Brian Kushner, MD    212-639-6793      
Contact: Nai-Kong Cheung, MD, PhD    646-888-2313      
Principal Investigator: Brian Kushner, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Brian Kushner, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02100930     History of Changes
Other Study ID Numbers: 13-260
Study First Received: March 27, 2014
Last Updated: March 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Anti-GD2 3F8 Monoclonal Antibody
oral isotretinoin
GM-CSF
Sargramostim
13-260

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Isotretinoin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014