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Trial record 2 of 17 for:    neuroblastoma, IL2

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00082758
Recruitment Status : Completed
First Posted : May 19, 2004
Results First Posted : January 16, 2014
Last Update Posted : February 12, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE May 14, 2004
First Posted Date  ICMJE May 19, 2004
Results First Submitted Date  ICMJE December 2, 2013
Results First Posted Date  ICMJE January 16, 2014
Last Update Posted Date February 12, 2015
Study Start Date  ICMJE August 2005
Actual Primary Completion Date February 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2015)
Number of Responders (Response Rate) [ Time Frame: Up to 30 weeks ]
Response rate to hu14.18-Interleukin-2 in 3 separate strata of patients with recurrent or refractory neuroblastoma. Patients will have radiologic (CT/MRI) tumor and urine homovanillic acid (HVA)/vanillylmandelic acid (VMA) measurements. Patients with prior marrow involvement will have marrow assessments. Patients with MIBG+ (iodine-131-meta-iodobenzylguanidine) prior disease will have MIBG scans performed. For CT/MRI lesions, measureable disease is measured by the Response Evaluation Criteria In Solid Tumors (RECIST) from the National Cancer Institute. RECIST (v1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE hu14.18-Interleukin-2 Fusion Protein in Treating Young Patients With Recurrent or Refractory Neuroblastoma
Official Title  ICMJE A Phase II Study Of hu14.18-IL2 In Children With Recurrent Or Refractory Neuroblastoma
Brief Summary

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.

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 (meta-iodobenzylguanidine) scanning and/or bone marrow histology vs disease identified and quantified by bone marrow immunohistochemistry).

For standard radiographic criteria this study will use the definitions of measurable disease from the Response Evaluation Criteria In Solid Tumors (RECIST) from the National Cancer Institute. Complete Response (CR) - Disappearance of all target lesions. No evidence of tumor at any site (chest, abdomen, liver, bone, bone marrow, nodes, etc). Very Good Partial Response (VGPR) - Greater than 90% decrease of the disease measurement for CT/MRI target lesions, taking as reference the disease measurement done to confirm measurable disease in target lesions at study entry; all pre-existing bone lesions with CR by MIBG; MIBG scan can be SD or CR in soft tissue lesions corresponding to lesions on CT/MRI. Partial Response (PR) - At least a 30% decrease in the disease measurement for CT/MRI target lesions, taking as reference the disease measurement done to confirm measurable disease in target lesions at study entry. Progressive Disease (PD) - Any one of the following: a) At least a 20% increase in the disease measurement for CT/MRI target lesions, taking as reference the smallest disease measurement recorded since the start of treatment. b) Appearance of one or more new lesions or new sites of tumor. c) PD as defined above for either bone marrow or MIBG lesions.

Stable disease (SD) - The patient will be classified as stable disease for overall response if there is stable disease by either CT/MRI lesion, bone marrow, or MIBG criteria. No new lesions; no new sites of disease.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Disease Measurable by Standard Criteria(hu14.18-interleukin-2)

    Patients with residual/refractory neuroblastoma and readily measurable residual/refractory disease using standard radiographic criteria. Standard radiographic criteria for CT/MRI Lesions will use the definitions of measurable disease from the Response Evaluation Criteria In Solid Tumors (RECIST) from the National Cancer Institute.

    hu14.18-Interleukin-2 fusion protein : Given IV

    Intervention: Biological: hu14.18-Interleukin-2 fusion protein
  • Experimental: Disease Eval by MIBG or BM Histology (hu14.18-interleukin-2)

    Patients with residual/refractory neuroblastoma with disease that is not measurable by standard radiographic criteria, but is evaluable by meta-iodobenzylguanidine (MIBG) scanning and/or by bone marrow (BM) histology.

    hu14.18-Interleukin-2 fusion protein : Given IV

    Intervention: Biological: hu14.18-Interleukin-2 fusion protein
  • Experimental: Disease Identified by BM Immunohistochemistry Only

    Patients with residual/refractory neuroblastoma that do not have disease that is measurable by standard radiographic techniques or evaluable by meta-iodobenzylguanidine (MIBG) scanning or bone marrow (BM) histology, however, disease is identified and quantified by BM immunohistochemistry (>5 neuroblastoma cells per 1,000,000 nucleated marrow cells).

    hu14.18-Interleukin-2 fusion protein : Given IV

    Intervention: Biological: hu14.18-Interleukin-2 fusion protein
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 7, 2013)
39
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date February 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (meta-iodobenzylguanidine) scanning
    • Immunocytochemistry
  • No symptomatic pleural effusions or ascites requiring constant or intermittent drainage
  • No clinical or radiological evidence of central nervous system (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

  • Alanine transaminase (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 Multi Gated Acquisition Scan (MUGA)
  • No symptomatic congestive heart failure
  • No uncontrolled cardiac rhythm disturbance

Pulmonary

  • Pulse oximetry > 94% on room air
  • Forced vital capacity (FVC) > 80%
  • Forced expiratory volume (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries Australia,   Netherlands,   New Zealand,   Puerto Rico,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT00082758
Other Study ID Numbers  ICMJE ANBL0322
CDR0000360723 ( Other Identifier: Clinical Trials.gov )
COG-ANBL0322 ( Other Identifier: Children's Oncology Group )
NCI-2012-02583 ( Other Identifier: NCI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Paul M Sondel, MD, PhD University of Wisconsin, Madison
Study Chair: Suzanne Shusterman, MD Dana-Farber Cancer Institute
PRS Account Children's Oncology Group
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP