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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005576
First received: May 2, 2000
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Disseminated Neuroblastoma
Recurrent Neuroblastoma
Regional Neuroblastoma
Biological: monoclonal antibody Ch14.18
Drug: isotretinoin
Biological: aldesleukin
Biological: sargramostim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: 32 days ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: January 2001
Primary Completion Date: March 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: monoclonal antibody Ch14.18
Given IV
Other Names:
  • Ch14.18
  • MOAB Ch14.18
Drug: isotretinoin
Given orally
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret
Biological: aldesleukin
Given IV
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Biological: sargramostim
Given IV
Other Names:
  • GM-CSF
  • Leukine
  • Prokine

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005576

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Andrew Gilman Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005576     History of Changes
Other Study ID Numbers: NCI-2012-01527, 0935, CDR0000063533
Study First Received: May 2, 2000
Last Updated: January 15, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
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
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Aldesleukin
Interleukin-2
Isotretinoin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 16, 2014