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

NCT01183416 | Completed Phase 2 Results DMC

• 1 other identifier: 09-158
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuroblastoma

Keywords

GM-CSF; MAB 3F8; RETINOIC ACID (CIS-9 & 13); 09-158

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (2)

• Apply Real-time Quantitative RT-PCR to Test the Hypothesis That the Minimal Residual Disease Content of Bone Marrow

  2 years

• Monitor Safety of the High-dose Antibody Treatment

  2 years

Study Arms (1)

3F8 monoclonal antibody and 13-cis-Retinoic Acid

EXPERIMENTAL

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.

Drug: 3F8 monoclonal antibody and 13-cis-Retinoic Acid

Interventions

3F8 monoclonal antibody and 13-cis-Retinoic Acid DRUG

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.

3F8 monoclonal antibody and 13-cis-Retinoic Acid

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, 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.

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 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

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

Interventions

Isotretinoin

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

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Dr. 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 17, 2010
• Study Start: August 1, 2010
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: October 9, 2019
• Results First Posted: October 9, 2019

Record last verified: 2018-10

Locations

US (1)