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

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 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.

Condition	Intervention	Phase
Neuroblastoma	Drug: 3F8 monoclonal antibody and 13-cis-Retinoic Acid	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 Consolidation of First Remission After Myeloablative Therapy and Autologous Stem-Cell Transplantation in Patients With High-Risk Neuroblastoma: A Phase II Study

Resource links provided by NLM:

Genetics Home Reference related topics: neuroblastoma

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 impact of high-dose 3F8/GM-CSF on relapse-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
in patients who are post-stem-cell transplantation and in first complete or very good partial remission, but at high risk of relapse.

Secondary Outcome Measures:

Apply real-time quantitative RT-PCR to test the hypothesis that the minimal residual disease content of bone marrow [ Time Frame: 2 years ] [ Designated as safety issue: No ]
after the first treatments with 3F8/GMCSF has significant prognostic impact on relapse-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:	43
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 monoclonal antibody and 13-cis-Retinoic Acid 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 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.

Arms

Assigned Interventions

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

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

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.

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, 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.

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183416

Locations

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

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:	NCT01183416 History of Changes
Other Study ID Numbers:	09-158
Study First Received:	August 16, 2010
Last Updated:	December 13, 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)
09-158

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

Antibodies, Monoclonal
Isotretinoin
Tretinoin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses
Antineoplastic Agents
Keratolytic Agents

ClinicalTrials.gov processed this record on May 21, 2013