Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Monoclonal Antibody Therapy With Sargramostim and Interleukin-2 in Treating Children With Neuroblastoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	21 and under	NCI	COG-A0935A CCG-0935, CCG-0935A, NCT00005576

Objectives

I. Determine the maximum tolerated dose of monoclonal antibody (MOAB) Ch14.18 
when combined with sargramostim (GM-CSF) and interleukin-2 (IL-2) after 
autologous bone marrow or peripheral blood stem cell rescue in children with 
neuroblastoma.

II. Determine the toxic effects of this regimen in these patients.

III. Determine the pharmacokinetics, including antibody level, 
antibody-binding activity, and presence of human anti-chimeric antibodies, of 
this regimen in these patients.

IV. Determine the activity of IL-2 and MOAB Ch14.18 against tumor cells in 
terms of response using standard clinical measurements such as bone marrow 
immunocytology in these patients.

V. Determine the extent of coating of tumor cells (bone marrow metastases) by 
MOAB Ch14.18 in these patients.

VI. Determine the feasibility of isotretinoin administered between courses 
beginning after course 2 in these patients.

Entry Criteria

Disease Characteristics:

Diagnosis of neuroblastoma based on tumor histology or bone marrow
metastasis with elevated urine catecholamine metabolites
 Confirmation of GD2-positivity not required 

Must have recently completed a course of myeloablative therapy followed by
autologous bone marrow or peripheral blood stem cell (PBSC) rescue

May be eligible:
 After completion of the third course of high-dose chemotherapy with PBSC
  rescue on protocol CCG-3951
 After completion of 1 or more courses of high-dose chemotherapy with PBSC
  rescue on an institutional (local) protocol 
 
Previous treatment on phase I studies (e.g., CCG-3951) allowed
 
Ineligible if evaluable for response on a Phase II/III protocol (e.g.,
CCG-6921, CCG-3891) 
 Patients who are no longer evaluable for response on a Phase II/III protocol
  (i.e., disease progression after therapy) are allowed

Prior/Concurrent Therapy:

Biologic Therapy:
 See Disease Characteristics
 No prior monoclonal antibody (MOAB) 14G2A or MOAB Ch14.18
 No other concurrent cytokines or growth factors (e.g., interferon or
  filgrastim (G-CSF))

Chemotherapy:
 See Disease Characteristics
 At least 2 weeks since prior myelosuppressive chemotherapy
 No other concurrent anticancer chemotherapy 
 
Endocrine therapy:
 At least 2 weeks since prior corticosteroids 
 No concurrent corticosteroids

Radiotherapy:
 At least 7 days since prior radiotherapy
 No concurrent radiotherapy except for localized painful lesions 

Surgery:
 Not specified

Other:
 At least 2 weeks since prior immunosuppressive drugs
 At least 2 weeks since prior tretinoin
 No concurrent immunosuppressive drugs (e.g., cyclosporine)
 No concurrent pentoxifylline

Patient Characteristics:

Age:
 21 and under

Performance status:
 0-2

Life expectancy:
 At least 2 months

Hematopoietic:
 Absolute phagocyte count (neutrophils and monocytes) greater than 1,000/mm3 

Hepatic:
 Bilirubin no greater than 1.5 times normal
 SGOT or SGPT no greater than 5.0 times normal
 Concurrent veno-occlusive disease allowed if stable or improving

Renal:
 Creatinine no greater than 1.5 times normal OR
 Creatinine clearance or radioisotope glomerular filtration rate at least 60
  mL/min

Cardiovascular:
 Shortening fraction at least 27% by echocardiogram OR
 Ejection fraction greater than 50% by MUGA scan

Pulmonary:
 FEV1 and FVC greater than 60% predicted OR
 For children who cannot perform pulmonary function tests:
  No evidence of dyspnea at rest
  No exercise intolerance
  Oxygen saturation greater than 94% on room air by pulse oximetry
 
Other:
 No CNS toxicity greater than grade 1
 Concurrent seizure disorder allowed if on anticonvulsants and well controlled
 

Expected Enrollment

Approximately 6-16 patients will be accrued for this study within 1 year.

Outline

This is a multicenter, dose-escalation study of monoclonal antibody (MOAB) 
Ch14.18.

Patients receive MOAB Ch14.18 IV over 5 hours on days 7-10 during courses 2 
and 4 and on days 3-6 during courses 1, 3, and 5; sargramostim (GM-CSF) IV 
over 2 hours or subcutaneously daily on days 0-13 during courses 1, 3, and 5; 
interleukin-2 IV continuously on days 0-3 and 7-10 during courses 2 and 4; and 
oral isotretinoin twice daily on days 14-27 during courses 2 and 4 and on days 
10-23 during courses 3 and 5. Treatment repeats every 24-32 days for 5 courses 
in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MOAB Ch14.18 until the 
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose 
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting 
toxicity. A minimum of 6 additional patients are treated at the MTD. 

Patients are followed every other week for 2 months and then every 3 months 
for 6 months.

Gilman AL, Ozkaynak MF, Matthay KK, et al.: Phase I study of ch14.18 with granulocyte-macrophage colony-stimulating factor and interleukin-2 in children with neuroblastoma after autologous bone marrow transplantation or stem-cell rescue: a report from the Children's Oncology Group. J Clin Oncol 27 (1): 85-91, 2009.[PUBMED Abstract]

Ozkaynak MF, Sondel PM, Krailo MD, et al.: Phase I study of chimeric human/murine anti-ganglioside G(D2) monoclonal antibody (ch14.18) with granulocyte-macrophage colony-stimulating factor in children with neuroblastoma immediately after hematopoietic stem-cell transplantation: a Children's Cancer Group Study. J Clin Oncol 18 (24): 4077-85, 2000.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Andrew Gilman, MD, Protocol chair(Contact information may not be current)		Ph: 816-234-3265 Email: agilman@cmh.edu

Registry Information
Official Title		A PHASE I STUDY OF CHIMERIC HUMAN/MURINE ANTI-GD2 MONOCLONAL ANTIBODY (ch14.18) WITH GM-CSF IN CHILDREN WITH NEUROBLASTOMA AND OTHER GD2 POSITIVE MALIGNANCIES IMMEDIATELY POST AUTOLOGOUS BMT
Trial Start Date		2001-01-11
Registered in ClinicalTrials.gov		NCT00005576
Date Submitted to PDQ		1994-05-27
Information Last Verified		2008-12-11
NCI Grant/Contract Number		CA57746

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