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

NCT01183897 | Completed Phase 2 Results DMC

• 1 other identifier: 09-161
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuroblastoma

Keywords

GM-CSF; MAB 3F8; RETINOIC ACID (CIS-9 & 13); 09-161

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (2)

• Apply Real-time Quantitative RT-PCR

  2 years

• Monitor Safety of the High-dose Antibody Treatment

  2 years

Study Arms (1)

3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic

EXPERIMENTAL

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).

Biological: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic

Interventions

3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic BIOLOGICAL

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.

3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 23633099 DERIVED

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Neuroblastoma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Brian Kushner MD
• Organization: Memorial Sloan Kettering Cancer Center

kushnerb@mskcc.org

212-639-6793

Study Officials

• Brian Kushner, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2010
• First Posted: August 18, 2010
• Study Start: August 12, 2010
• Primary Completion: September 25, 2018
• Study Completion: September 25, 2018
• Last Updated: August 13, 2019
• Results First Posted: August 13, 2019

Record last verified: 2018-09

Locations

US (1)