High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01183897

Purpose

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 you and your cancer. The investigators also want to see if the antibody works against a very small amount of neuroblastoma (minimal residual disease)that could be left in your bone marrow.

Condition	Intervention	Phase
Neuroblastoma	Biological: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow: A Phase II Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Tretinoin Isotretinoin Sargramostim

U.S. FDA Resources

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

Primary Outcome Measures:

Assess the activity of high-dose 3F8/GM-CSF [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
to assure no side-effects or noxious sequelae develop or emerge that were not seen in the prior phase I study.

Estimated Enrollment:	53
Study Start Date:	August 2010
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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. The patients have primary refractory BM disease. Protocol treatment is through 24 months. Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. 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.

Arms

Assigned Interventions

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. The patients have primary refractory BM disease. Protocol treatment is through 24 months. Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. 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.

Eligibility

Ages Eligible for Study:	18 Months and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183897

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:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01183897 History of Changes
Other Study ID Numbers:	09-161
Study First Received:	August 16, 2010
Last Updated:	April 18, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

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

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
Isotretinoin
Tretinoin
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Keratolytic Agents

ClinicalTrials.gov processed this record on May 23, 2012