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A PHASE I STUDY OF CHIMERIC HUMAN/MURINE ANTI-GD2 MONOCLONAL ANTIBODY (ch14.18) WITH GM-CSF AND INTERLEUKIN-2 (IL-2) IN CHILDREN WITH NEUROBLASTOMA IMMEDIATELY POST AUTOLOGOUS BMT OR PBSC RESCUE


Phase 1
N/A
21 Years
Not Enrolling
Both
Disseminated Neuroblastoma, Recurrent Neuroblastoma, Regional Neuroblastoma

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Trial Information

A PHASE I STUDY OF CHIMERIC HUMAN/MURINE ANTI-GD2 MONOCLONAL ANTIBODY (ch14.18) WITH GM-CSF AND INTERLEUKIN-2 (IL-2) IN CHILDREN WITH NEUROBLASTOMA IMMEDIATELY POST AUTOLOGOUS BMT OR PBSC RESCUE


PRIMARY 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.

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

Patients receive MOAB 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 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.

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


Inclusion Criteria:



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

- Patients must have a diagnosis of neuroblastoma based upon tumor histology or bone
marrow metastases and elevated urine catecholamine metabolites; greater than 98% of
neuroblastomas are GD2-positive without intratumor heterogeneity, so these tumors
will not be immunostained prior to study entry

- Patients entered on CCG-3951 may become eligible following the third course of
high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue; patients
treated on institutional (local) protocols of high-dose chemotherapy with PBSC rescue
may also become eligible after one or more courses of PBSC rescue

- Patients must enter onto study within 8 weeks after the total absolute phagocyte
count [neutrophils (segs + bands) + monocytes] is > 1,000/uL; the APC criteria
include counts obtained while on G-CSF therapy

- Patients must have a performance status of 0, 1 or 2 and patients must have a life
expectancy of >= 2 months

- Serum creatinine =< 1.5 x normal, or creatinine clearance or radioisotope glomerular
filtration rate (GFR) >= 60 ml/min/1.73 m^2

- Total bilirubin =< 1.5 x normal

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x
normal

- Veno-occlusive disease, if present, should be stable or improving

- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by
gated radionuclide study

- Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) > 60% of
predicted by pulmonary function test

- For children who are unable to do pulmonary function tests (PFTs), no evidence of
dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% on room air

- Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled

- Central nervous system (CNS) toxicity < grade 2

- Patients must have a double lumen catheter or single lumen and peripheral IV so that
interleukin (IL)-2 and ch14.18 can be given separately

- Patients who remain evaluable for response on Phase II/III studies (i.e. CCG-3891)
are not eligible for this study; however, patients treated on Phase I studies (i.e.
CCG-3951) and patients who are no longer evaluable on Phase II/III studies (i.e.
progressive disease following therapy) will be eligible

- Patients who were previously treated with antibody 14.G2a or ch14.18 are ineligible
for this study

- Patients requiring chronic use of corticosteroids are ineligible

- Corticosteroid, immunosuppressive drugs, myelosuppressive chemotherapy, and retinoic
acid must not be given within 14 days prior to study entry

- Radiation therapy must not be given within seven days prior to study entry or during
therapy

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, FDA, and NCI requirements for human studies must be met

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of monoclonal antibody (MOAB) ch14.18 when combined with sargramostim and IL-2 after autologous bone marrow or peripheral blood stem cell rescue in children with neuroblastoma

Outcome Time Frame:

32 days

Safety Issue:

Yes

Principal Investigator

Andrew Gilman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

NCI-2012-01527

NCT ID:

NCT00005576

Start Date:

January 2001

Completion Date:

Related Keywords:

  • Disseminated Neuroblastoma
  • Recurrent Neuroblastoma
  • Regional Neuroblastoma
  • Neuroblastoma

Name

Location

Children's Oncology GroupArcadia, California  91006-3776