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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, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.


Condition or disease Intervention/treatment Phase
Neuroblastoma Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 340 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Anti-GD2 3F8 Antibody and GM-CSF for High-Risk Neuroblastoma
Study Start Date : July 2003
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. Efficacy at completion of treatment [ Time Frame: 3 years ]
  2. Relapse-free survival every 3 months [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Compare granulocyte activation in patients treated with short-term vs prolonged daily exposure to sargramostim (GM-CSF) after 4 courses [ Time Frame: 3 years ]
  2. Simplify treatment with consequent reduction in cost [ Time Frame: 3 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00072358


Locations
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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Brian H. Kushner, MD Memorial Sloan Kettering Cancer Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00072358     History of Changes
Other Study ID Numbers: 03-077
MSKCC-03077
First Posted: November 6, 2003    Key Record Dates
Last Update Posted: October 4, 2018
Last Verified: October 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:
disseminated neuroblastoma
localized unresectable neuroblastoma
recurrent neuroblastoma
regional neuroblastoma
stage 4S neuroblastoma

Additional relevant MeSH terms:
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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
Carbamide Peroxide
Antineoplastic Agents, Immunological
Temozolomide
Isotretinoin
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Sargramostim
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Anti-Infective Agents, Local
Anti-Infective Agents