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NeuroblastomaPhase 2NCT00082758

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

A Phase 2 study testing hu14.18-Interleukin-2 fusion protein in people with Neuroblastoma, run by Children's Oncology Group at 81 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
Neuroblastoma
What is being tested?
hu14.18-Interleukin-2 fusion protein
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
81 sitesin 2 countries
Study dates
Aug 2005to May 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

81 sites in 2 countries.

81 sites in 2 countries

United States69 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308-1062

  • University of New Mexico Cancer Research and Treatment Center

    Albuquerque, New Mexico, 87131-5636

  • Tulane Cancer Center Office of Clinical Research

    Alexandria, Louisiana, 71315-3198

  • Texas Tech University Health Sciences Center School of Medicine - Amarillo

    Amarillo, Texas, 79106

  • MBCCOP - Medical College of Georgia Cancer Center

    Augusta, Georgia, 30912-3730

  • CancerCare of Maine at Eastern Maine Medial Center

    Bangor, Maine, 04401

  • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

    Birmingham, Alabama, 35294

  • Floating Hospital for Children at Tufts - New England Medical Center

    Boston, Massachusetts, 02111

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • Presbyterian Cancer Center at Presbyterian Hospital

    Charlotte, North Carolina, 28233-3549

  • T.C. Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Palmetto Health South Carolina Cancer Center

    Columbia, South Carolina, 29203

  • Columbus Children's Hospital

    Columbus, Ohio, 43205-2696

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822-0001

  • Children's Hospital Cancer Center

    Denver, Colorado, 80218-1088

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Spectrum Health Hospital - Butterworth Campus

    Grand Rapids, Michigan, 49503-2560

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • University of Mississippi Cancer Clinic

    Jackson, Mississippi, 39216-4505

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Children's Hospital

    Knoxville, Tennessee, 37901

  • Breslin Cancer Center at Ingham Regional Medical Center

    Lansing, Michigan, 48910

  • Sunrise Hospital and Medical Center

    Las Vegas, Nevada, 89109-2306

  • Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

  • Markey Cancer Center at University of Kentucky Chandler Medical Center

    Lexington, Kentucky, 40536-0293

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Children's Hospital Central California

    Madera, California, 93638-8762

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Overlook Hospital

    Morristown, New Jersey, 07962

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08903

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Sacred Heart Cancer Center at Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-9786

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • Carilion Cancer Center of Western Virginia

    Roanoke, Virginia, 24029

  • Sutter Cancer Center

    Sacramento, California, 95816

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113-1100

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78207

  • UCSF Comprehensive Cancer Center

    San Francisco, California, 94115

  • Providence Cancer Center at Sacred Heart Medical Center

    Spokane, Washington, 99220-2555

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62794-9620

  • Siteman Cancer Center at Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Stanford Comprehensive Cancer Center - Stanford

    Stanford, California, 94305

  • St. Joseph's Cancer Institute at St. Joseph's Hospital

    Tampa, Florida, 33607

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

  • Kaplan Cancer Center at St. Mary's Medical Center

    West Palm Beach, Florida, 33407

Other trials in United States

Canada12 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 1Z2

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Children's Hospital of Western Ontario

    London, Ontario, N6A 4G5

  • Montreal Children's Hospital at McGill University Health Center

    Montreal, Quebec, H3H 1P3

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • Centre Hospitalier Universitaire de Quebec

    Québec, G1V 4G2

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • Children's & Women's Hospital of British Columbia

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Phase II Study Of hu14.18-IL2 In Children With Recurrent Or Refractory Neuroblastoma

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.

Read the 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.

Conditions
Neuroblastoma
Being tested
hu14.18-Interleukin-2 fusion protein
Keywords
recurrent neuroblastoma
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • hu14.18-Interleukin-2 fusion proteinBiological

    Also called IMMUNOCYTOKINE HU14.18-IL2 FUSION PROTEIN, humanized anti GD2 antibody fused with human IL-2, BB-IND-9798

    Given IV

Study groups in NCT00082758
Study groupRoleWhat they receive
Disease Measurable by Standard Criteria(hu14.18-interleukin-2)ExperimentalPatients 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
Receives: Biological: hu14.18-Interleukin-2 fusion protein
Disease Eval by MIBG or BM Histology (hu14.18-interleukin-2)ExperimentalPatients 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
Receives: Biological: hu14.18-Interleukin-2 fusion protein
Disease Identified by BM Immunohistochemistry OnlyExperimentalPatients 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
Receives: Biological: hu14.18-Interleukin-2 fusion protein

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Responders (Response Rate)

    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.

    Measured: Up to 30 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2004 (estimated)
  2. Study startAug 2005
  3. Primary completionFeb 2008
  4. Study completionMay 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00082758
Sponsor's protocol ID
ANBL0322
Other IDs
CDR0000360723, COG-ANBL0322, NCI-2012-02583
Status last verified
Jan 2015
First submitted
14 May 2004
Last updated
12 Feb 2015
Data monitoring committee
Yes

Publications

  • Delgado DC, Hank JA, Kolesar J, Lorentzen D, Gan J, Seo S, Kim K, Shusterman S, Gillies SD, Reisfeld RA, Yang R, Gadbaw B, DeSantes KB, London WB, Seeger RC, Maris JM, Sondel PM. Genotypes of NK cell KIR receptors, their ligands, and Fcgamma receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res. 2010 Dec 1;70(23):9554-61. doi: 10.1158/0008-5472.CAN-10-2211. Epub 2010 Oct 8.

    PubMed 20935224

  • Shusterman S, London WB, Gillies SD, Hank JA, Voss SD, Seeger RC, Reynolds CP, Kimball J, Albertini MR, Wagner B, Gan J, Eickhoff J, DeSantes KB, Cohn SL, Hecht T, Gadbaw B, Reisfeld RA, Maris JM, Sondel PM. Antitumor activity of hu14.18-IL2 in patients with relapsed/refractory neuroblastoma: a Children's Oncology Group (COG) phase II study. J Clin Oncol. 2010 Nov 20;28(33):4969-75. doi: 10.1200/JCO.2009.27.8861. Epub 2010 Oct 4.

    PubMed 20921469

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing hu14.18-Interleukin-2 fusion protein in people with Neuroblastoma, run by Children's Oncology Group at 81 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 81 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Responders (Response Rate) (time frame: Up to 30 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00082758, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2015.

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