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

3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow: A Phase II Study

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.

Study Overview

• Status: Completed
• Conditions: Neuroblastoma
• Intervention / Treatment: Biological: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years
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.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 12, 2010
• Primary Completion (ACTUAL): September 25, 2018
• Study Completion (ACTUAL): September 25, 2018

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: August 17, 2010
• First Posted (ESTIMATE): August 18, 2010

Study Record Updates

• Last Update Posted (ACTUAL): August 13, 2019
• Last Update Submitted That Met QC Criteria: July 24, 2019
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: GM-CSF; MAB 3F8; RETINOIC ACID (CIS-9 & 13); 09-161
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma
• Other Study ID Numbers: 09-161