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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01183897
First received: August 16, 2010
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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.


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: 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:


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 2015
Estimated Primary Completion Date: August 2015 (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.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.


  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. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: October 15, 2014
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
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Isotretinoin
Tretinoin
Antineoplastic Agents
Dermatologic Agents
Keratolytic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014