hu14.18-Interleukin-2 Fusion Protein in Treating Young Patients With Recurrent or Refractory Neuroblastoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00082758
First received: May 14, 2004
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein work in different ways to stimulate the immune system and stop tumor cells from growing.

PURPOSE: This phase II trial is studying how well hu14.18-interleukin-2 fusion protein works in treating young patients with recurrent or refractory neuroblastoma.


Condition Intervention Phase
Neuroblastoma
Biological: hu14.18-Interleukin-2 fusion protein
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of hu14.18-IL2 In Children With Recurrent Or Refractory Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Best Overall Response (Complete Response, Very Good Partial Response, or Partial Response) [ Time Frame: Up to 10 courses or about 30 weeks ] [ Designated as safety issue: No ]
    Proportion of responders within each stratum. Measurable disease determined by RECIST (Response Evaluation Criteria In Solid Tumors Criteria). Patient's response is assessed after completion of 10 courses. The central review of MIBG scans were used for the evaluation of overall response. Complete Response (CR) is the disappearance of all target lesions. Very Good Partial Response (VGPR) is >90% decrease of the disease measurement for CT/MRI target lesions. Partial Response (PR) is >=30% decrease in the sum of the longest diameter of CT/MRI target lesions. Patients deemed inevaluable for response have response data tabulated and reported descriptively, but will not be counted in the target accrual for response for each strata. Patients with disease measureable by bone marrow immunohistochemistry are tabulated and reported but not included in the statistical analysis to determine activity of hu14.18-IL2 as insufficient data to support the significance of immunocytologic responses.


Enrollment: 39
Study Start Date: August 2005
Study Completion Date: May 2012
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Disease Measurable by CT or MRI scan (hu14.18-interleukin-2)
Stratum 01 includes patients with residual/refractory neuroblastoma and readily measurable residual/refractory disease using standard radiographic criteria. Treatment (hu14.18-interleukin-2 fusion protein - dosage 12/mg/m2/day) on days 1,2,3 of 28 day cycle 1 - 10.
Biological: hu14.18-Interleukin-2 fusion protein
Given IV
Other Names:
  • IMMUNOCYTOKINE HU14.18-IL2 FUSION PROTEIN
  • humanized anti GD2 antibody fused with human IL-2
  • BB-IND-9798
Experimental: Disease eval by Bone Marrow or MIBG(hu14.18-interleukin-2)
Stratum 02 includes patients with residual/refractory neuroblastoma with disease that is not measurable by standard radiographic criteria, but is evaluable by MIBG scanning and/or by bone marrow histology. Treatment (hu14.18-interleukin-2 fusion protein - dosage 12/mg/m2/day) on days 1,2,3 of 28 day cycle 1 - 10.
Biological: hu14.18-Interleukin-2 fusion protein
Given IV
Other Names:
  • IMMUNOCYTOKINE HU14.18-IL2 FUSION PROTEIN
  • humanized anti GD2 antibody fused with human IL-2
  • BB-IND-9798
Experimental: Measured by BM immunohistochemistry (hu14.18-interleukin-2)
Stratum 03 includes patients with residual/refractory neuroblastoma that do not have disease that is measurable by standard radiographic techniques or evaluable by MIBG scanning or bone marrow histology, however, disease is identified and quantified by bone marrow (BM) immunohistochemistry (>5 neuroblastoma cells per 1,000,000 nucleated marrow cells). Treatment (hu14.18-interleukin-2 fusion protein - dosage 12/mg/m2/day) on days 1,2,3 of 28 day cycle 1 - 10.
Biological: hu14.18-Interleukin-2 fusion protein
Given IV
Other Names:
  • IMMUNOCYTOKINE HU14.18-IL2 FUSION PROTEIN
  • humanized anti GD2 antibody fused with human IL-2
  • BB-IND-9798

Detailed Description:

OBJECTIVES:

  • Determine the response rate in children with recurrent or refractory neuroblastoma treated with hu14.18-interleukin-2 (hu14.18-IL2) fusion protein.
  • Determine the adverse events of this drug in these patients.
  • Determine the immunologic activation in patients treated with this drug.
  • Determine the induction of anti-hu14.18-IL2 antibody in patients treated with this drug.
  • Correlate antitumor response with measurements of toxicity, immune activation, and anti-hu14.18-IL2 antibody activity in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to measurable/evaluable disease (measurable by standard radiographic criteria vs evaluable by MIBG scanning and/or bone marrow histology vs disease identified and quantified by bone marrow immunohistochemistry).

Patients will be enrolled in 3 strata, and evaluated for antitumor response following 2 monthly courses (treatment on Days 1-3, followed by 25 days of observation,). Patients with progressive disease will be taken off protocol therapy. Patients with stabilization or regression of disease will be eligible to receive 2 more monthly courses of treatment. Additional treatment following course 4 will be allowed for patients showing a continued clinical response, up to a maximum of 10 courses of treatment.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 40-60 patients (20 for strata 1 and 2 and 0-20 for stratum 3) will be accrued for this study within 2 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed neuroblastoma
  • Relapsed or refractory to conventional therapy
  • Measurable or evaluable disease documented by 1 of the following criteria:

    • Clinical
    • Radiographic
    • Histologic
    • MIBG scanning
    • Immunocytochemistry
  • No symptomatic pleural effusions or ascites requiring constant or intermittent drainage
  • No clinical or radiological evidence of CNS disease

PATIENT CHARACTERISTICS:

Age

  • 21 and under

Performance status

  • Karnofsky 50-100% (> 16 years of age)
  • Lansky 50-100% (≤ 16 years of age)

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3*

    • Must not be refractory to platelet transfusions
  • Hemoglobin ≥ 9.0 g/dL* NOTE: *Transfusion allowed if patient is known to have a history of bone marrow involvement with tumor

Hepatic

  • ALT < 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • Hepatitis B surface antigen negative

Renal

  • Creatinine adjusted according to age as follows:

    • No greater than 0.4 mg/dL (≤ 5 months)
    • No greater than 0.5 mg/dL (6 months -11 months)
    • No greater than 0.6 mg/dL (1 year-23 months)
    • No greater than 0.8 mg/dL (2 years-5 years)
    • No greater than 1.0 mg/dL (6 years-9 years)
    • No greater than 1.2 mg/dL (10 years-12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 years to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male]) OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Cardiovascular

  • Shortening fraction ≥ 27% by echocardiogram OR
  • Ejection fraction ≥ 50% by MUGA
  • No symptomatic congestive heart failure
  • No uncontrolled cardiac rhythm disturbance

Pulmonary

  • Pulse oximetry > 94% on room air
  • FVC > 80%
  • FEV_1 > 80%
  • No abnormal respiratory function
  • No dyspnea at rest
  • No exercise intolerance
  • No prior history of ventilator support related to lung injury (e.g., pneumonia, hemorrhagic pneumonitis, or capillary leakage)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No active uncontrolled infection
  • No active uncontrolled peptic ulcer
  • No objective peripheral neuropathy ≥ grade 2
  • No significant psychiatric disabilities
  • No seizure disorders requiring antiseizure medications
  • No other concurrent significant illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Recovered from prior immunotherapy
  • Prior in vivo monoclonal antibodies for biologic therapy or tumor imaging allowed provided there is documented absence of detectable antibody to hu14.18 by serology
  • More than 28 days since prior autologous stem cell transplantation

    • Prior autologous marrow or stem cell infusion using monoclonal antibody-purged specimens allowed
  • More than 1 week since prior growth factors
  • At least 7 days since prior nonmyelosuppressive biologic agents
  • No prior allogeneic bone marrow or stem cell transplantation
  • No concurrent immunomodulating agents
  • No concurrent growth factors

Chemotherapy

  • More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
  • No concurrent anticancer chemotherapy

Endocrine therapy

  • No concurrent corticosteroids except 100 mg or less of hydrocortisone (or equivalent) as premedication for blood transfusion or treatment for transfusion reaction

    • No other use of systemic steroids

Radiotherapy

  • Recovered from prior radiotherapy
  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • At least 6 months since prior craniospinal radiotherapy
  • At least 6 months since prior total body irradiation
  • At least 6 months since prior radiotherapy to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable or evaluable lesion is not irradiated

Surgery

  • More than 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy)
  • No prior organ allografts

Other

  • No concurrent immunosuppressive drugs
  • No other concurrent myelosuppressive antineoplastic drugs
  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: NCT00082758

  Show 81 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Paul M Sondel, MD, PhD University of Wisconsin, Madison
Study Chair: Suzanne Shusterman, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00082758     History of Changes
Other Study ID Numbers: ANBL0322, CDR0000360723, COG-ANBL0322, NCI-2012-02583
Study First Received: May 14, 2004
Results First Received: December 2, 2013
Last Updated: September 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent neuroblastoma

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
Denileukin diftitox
Interleukin-2
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 30, 2014