A Study of MAb-3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus 13-cis-Retinoic Acid (RA) Plus GM-CSF in Primary Refractory Neuroblastoma Patients

This study has been terminated.
(Lack of enrollment.)
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00969722
First received: August 31, 2009
Last updated: February 28, 2013
Last verified: February 2013
  Purpose

This is a multicenter, randomized, controlled, open-label study. Patients meeting inclusion/exclusion criteria will be randomized (1:1) to receive two cycles of MAb-3F8 plus GM-CSF or RA plus GM-CSF. Patients who do not respond to their assigned treatment after two cycles may cross-over to receive the alternate treatment. Disease response and safety will be assessed in all patients after cycle 2 and after cycle 4.


Condition Intervention Phase
Primary Refractory Neuroblastoma
Biological: MAb-3F8
Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
Biological: 13-cis-Retinoic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study of Monoclonal Antibody 3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Compared to 13-cis-Retinoic Acid Plus GM-CSF in High Risk Stage 4, Primary Refractory Neuroblastoma Patients

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • To compare the proportion of patients achieving a complete bone marrow response measured by an absence of histological evidence of bone marrow disease and by MIBG scan after two cycles of treatment. [ Time Frame: two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • A comparison in treatment arms for disease response as measured by CT/MRI scan and urine catecholamines, MIBG extent of disease scores, disease response in cross-over patients. [ Time Frame: two years ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: August 2009
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM I
Intravenous MAb-3F8 plus Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
Biological: MAb-3F8 Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
Active Comparator: ARM II
Oral 13-cis-Retinoic Acid (RA) plus Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Biological: 13-cis-Retinoic Acid

  Eligibility

Ages Eligible for Study:   18 Months to 13 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a diagnosis of stage 4 neuroblastoma diagnosed in accordance with the International Neuroblastoma Staging System: either (a) histologic confirmation which may involve immunohistochemical, ultrastructural, and/or cytogenetic studies, or (b) elevated urinary catecholamines plus tumor cells/clumps in the bone marrow.
  • Have evaluable disease or biopsy-proven stable disease in BM by histology or MIBG scan with MIBG-positive disease confined to the bone or bone marrow, plus urine catecholamine results, documented >3 weeks after conventional chemotherapy or >6 weeks after stem-cell transplantation. CT, MRI, or bone scan (if necessary) can be done at 2-3 weeks after conventional chemotherapy confirming that the chemotherapy, radiotherapy, and ABMT are not realistic curative options.
  • Be between 18 months to 13 years old at diagnosis.
  • Have recovered to grade 2 or better toxicities since their prior therapy.
  • Must, if female of childbearing potential, be willing to use two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at screening and monthly thereafter through the first four cycles of treatment.
  • Have a performance score of at least 60 from Lansky Play Performance Scale if aged up to 16 years or at least 60 from Karnofsky Scale if aged more than 16 years.
  • Have voluntarily agreed to participate.

Exclusion Criteria:

  • Have measurable disease ≥ 1 cm assessed by CT or MRI.
  • Have progressive disease (any new lesion; increase of any measurable lesion by >25%; or previous negative marrow positive for tumor).
  • Have disease detectable in CNS (confirmed by CT or MRI of the brain at screening or within 8 weeks of randomization).
  • Be receiving alternative therapy for the treatment of neuroblastoma, e.g. radiotherapy or chemotherapy within 3 weeks of randomization.
  • Require additional therapy (such as radiotherapy) during the first two treatment cycles.
  • Have detectable human anti-mouse antibody titers at screening.
  • Have received prior anti-GD2 investigational therapies.
  • Have a history of allergies to mouse proteins.
  • Have an active infection requiring IV infusion of antibiotics.
  • Be currently receiving long-term chronic treatment with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.
  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: NCT00969722

Locations
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
Rady Children's Hospital of San Diego
San Diego, California, United States, 92123
United States, District of Columbia
Georgetown Medical Center
Washington, District of Columbia, United States, 20057
United States, Florida
All Children's Hospital in Florida
St. Petersburg, Florida, United States, 33701
United States, Louisiana
LSU Health Sciences Center; Children's Hospital
New Orleans, Louisiana, United States, 70118
United States, Minnesota
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404
United States, New York
Children's Hospital at Montefiore
Bronx, New York, United States, 10467
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Nationwide Childrens Hospital
Columbus, Ohio, United States, 43205
United States, Oklahoma
University of Oklahoma Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
US Oncology
Dallas, Texas, United States, 75230
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84113
United States, Vermont
Vermont Cancer Center
Burlington, Vermont, United States, 05405
Sponsors and Collaborators
United Therapeutics
Investigators
Principal Investigator: Peter E. Zage, M.D. M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00969722     History of Changes
Other Study ID Numbers: 3F8-NB-201
Study First Received: August 31, 2009
Last Updated: February 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by United Therapeutics:
Neuroblastoma
3F8
Primary refractory

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 September 30, 2014