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

NCT ID: NCT00005576

Last Updated: 2013-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-01-31

Brief Summary

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Monoclonal antibodies 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. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining monoclonal antibody therapy with sargramostim or interleukin-2 may kill more tumor cells. Phase I trial to study the effectiveness of monoclonal antibody therapy given with sargramostim and interleukin-2 in treating children with neuroblastoma who have just completed bone marrow or peripheral stem cell transplantation

Detailed Description

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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.

Conditions

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Disseminated Neuroblastoma Recurrent Neuroblastoma Regional Neuroblastoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (monoclonal antibody Ch14.18, aldesleukin)

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.

Group Type EXPERIMENTAL

monoclonal antibody Ch14.18

Intervention Type BIOLOGICAL

Given IV

isotretinoin

Intervention Type DRUG

Given orally

aldesleukin

Intervention Type BIOLOGICAL

Given IV

sargramostim

Intervention Type BIOLOGICAL

Given IV

Interventions

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monoclonal antibody Ch14.18

Given IV

Intervention Type BIOLOGICAL

isotretinoin

Given orally

Intervention Type DRUG

aldesleukin

Given IV

Intervention Type BIOLOGICAL

sargramostim

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Ch14.18 MOAB Ch14.18 13-CRA Amnesteem Cistane Claravis Sotret IL-2 Proleukin recombinant human interleukin-2 recombinant interleukin-2 GM-CSF Leukine Prokine

Eligibility Criteria

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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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Gilman

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Oncology Group

Arcadia, California, United States

Site Status

Countries

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United States

Other Identifiers

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0935

Identifier Type: -

Identifier Source: secondary_id

CDR0000063533

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01527

Identifier Type: -

Identifier Source: org_study_id

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