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Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma

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ClinicalTrials.gov Identifier: NCT00072358
Recruitment Status : Active, not recruiting
First Posted : November 6, 2003
Last Update Posted : October 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE November 4, 2003
First Posted Date  ICMJE November 6, 2003
Last Update Posted Date October 4, 2019
Study Start Date  ICMJE July 2003
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 6, 2012)
  • Efficacy at completion of treatment [ Time Frame: 3 years ]
  • Relapse-free survival every 3 months [ Time Frame: 3 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00072358 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2012)
  • Compare granulocyte activation in patients treated with short-term vs prolonged daily exposure to sargramostim (GM-CSF) after 4 courses [ Time Frame: 3 years ]
  • Simplify treatment with consequent reduction in cost [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma
Official Title  ICMJE Phase II Study of Anti-GD2 3F8 Antibody and GM-CSF for High-Risk Neuroblastoma
Brief Summary

RATIONALE: Monoclonal antibodies, such as monoclonal antibody 3F8, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Combining monoclonal antibody 3F8 with sargramostim may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining monoclonal antibody 3F8 with sargramostim in treating patients who have neuroblastoma.

Detailed Description

OBJECTIVES:

  • Determine the efficacy of sargramostim (GM-CSF) in enhancing monoclonal antibody 3F8-mediated ablation in patients with high-risk neuroblastoma.
  • Determine the prognostic impact of minimal residual bone marrow disease on relapse-free survival of patients treated with this regimen.
  • Compare the effects of short-term (2-hour intravenous) vs prolonged (subcutaneous release) daily GM-CSF on granulocyte activation, in order to establish the optimal route for tumor-cell kill in these patients.

OUTLINE: This is an open-label study. Patients are stratified according to evaluable disease (yes [primary refractory bone marrow disease] vs no [no evidence of disease]).

Patients receive sargramostim (GM-CSF) subcutaneously on days -5 to 4 and monoclonal antibody 3F8 IV over 0.5-1.5 hours on days 0-4. Treatment repeats every 3 weeks for 4 courses and then every 8 weeks for up to a total of 24 months in the absence of disease progression or unacceptable toxicity.

Beginning after 2 courses of GM-CSF and monoclonal antibody 3F8, patients also receive oral isotretinoin twice daily on days 1-14 (when no monoclonal antibody 3F8 is administered). Treatment with isotretinoin repeats approximately every 28 days for 6 courses.

PROJECTED ACCRUAL: A total of 340 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE
  • Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
    The total dosage of 3F8 per cycle is the same as in prior trials (100 mg/m2), administered at 20 mg/m2/day and infused over ~1.5 hr or less (0.5 hr is customary), with analgesics and antihistamines used as needed for expected side-effects. 3F8 is started ~1 hr after completion of GM-CSF administration. GM-CSF is dosed at 250 mcg/m2/day from day -5 to day +1 (Wednesday to Tuesday is customary) , and is 500 mcg/m2/day thereafter (i.e., on days +2 to +4; Wednesday to Friday), as in the predecessor protocol.18,74 Patients come off study if progressive disease occurs or if there is life-threatening grade 4 toxicity from 3F8; otherwise, patients will receive a minimum of 4 cycles of treatment and will continue treatment through 24 months. It is expected that patients will receive ~10 cycles.
    Other Names:
    • patients (enrolled on study for treatment of primary refractory disease), the
    • break between end of a cycle of 3F8/GM-CSF and start of next cycle is 2-to-4-weeks through 4
    • cycles after achievement of CR in BM; subsequent breaks are ~8 weeks. In this
    • group, isotretinoin is started after documentation of response to, and after
    • >2 cycles of, 3F8/GM-CSF.
  • Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
    The total dosage of 3F8 per cycle is the same as in prior trials (100 mg/m2), administered at 20 mg/m2/day and infused over ~1.5 hr or less (0.5 hr is customary), with analgesics and antihistamines used as needed for expected side-effects. 3F8 is started ~1 hr after completion of GM-CSF administration. GM-CSF is dosed at 250 mcg/m2/day from day -5 to day +1 (Wednesday to Tuesday is customary) , and is 500 mcg/m2/day thereafter (i.e., on days +2 to +4; Wednesday to Friday), as in the predecessor protocol.18,74 Patients come off study if progressive disease occurs or if there is life-threatening grade 4 toxicity from 3F8; otherwise, patients will receive a minimum of 4 cycles of treatment and will continue treatment through 24 months. It is expected that patients will receive ~10 cycles.
    Other Names:
    • For Group 2 patients (enrolled on study in CR/VGPR, i.e., with no evidence of disease),
    • the break between end of a cycle and start of next cycle is 2-to-4 weeks through 4 cycles;
    • subsequent breaks are ~8 weeks. Isotretinoin is started after cycle 2 of 3F8/GM-CSF. Road
    • map/schema is in section 4.2. Regarding patients in second or greater CR from relapse in the
    • central nervous system, if they develop early HAMA which precludes timely completion of the
    • minimum of 4 cycles of 3F8/GM-CSF, they are eligible to go off protocol, to be treated with
    • low-dose maintenance regimens of irinotecan,94 temozolomide,95 or the two agents combined;96
    • they can resume treatment with 3F8/GM-CSF if HAMA becomes negative.
Study Arms  ICMJE
  • Experimental: patients have refractory bone marrow disease
    This phase II trial of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response of minimal residual disease (MRD) in patients with high-risk neuroblastoma (NB) and help establish the optimal way to use GM-CSF.
    Intervention: Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
  • Experimental: patients have no evidence of disease
    This phase II trial of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response of minimal residual disease (MRD) in patients with high-risk neuroblastoma (NB) and help establish the optimal way to use GM-CSF.
    Intervention: Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 14, 2010)
340
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of neuroblastoma by histopathology OR bone marrow metastases and high urine catecholamine levels
  • Disease must meet risk-related treatment guidelines and any of the following International Neuroblastoma Staging System stages:

    • Stage 4 with (any age) OR without (> 18 months of age of age) MYCN amplification
    • MYCN-amplified other than stage 1
  • No evidence of disease (i.e., in complete response/remission or very good partial response/remission) OR disease resistant to standard therapy (i.e., incomplete response in bone marrow)
  • No progressive disease or MIBG-avid soft tissue tumor

PATIENT CHARACTERISTICS:

  • No existing renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3
  • No human anti-mouse antibody (HAMA) titer greater than 1,000 Elisa units/mL
  • No history of allergy to mouse proteins
  • No active life-threatening infection
  • Not pregnant
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • Not specified
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00072358
Other Study ID Numbers  ICMJE 03-077
MSKCC-03077
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Brian H. Kushner, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP