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

NCT00082758 | Completed Phase 2 Results DMC

• 4 other identifiers: ANBL0322CDR0000360723COG-ANBL0322NCI-2012-02583
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 81

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.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma

Outcome Measures

Primary Outcomes (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.

  Up to 30 weeks

Study Arms (3)

Disease Measurable by Standard Criteria(hu14.18-interleukin-2)

EXPERIMENTAL

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

Biological: hu14.18-Interleukin-2 fusion protein

Disease Eval by MIBG or BM Histology (hu14.18-interleukin-2)

EXPERIMENTAL

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

Biological: hu14.18-Interleukin-2 fusion protein

Disease Identified by BM Immunohistochemistry Only

EXPERIMENTAL

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

Biological: hu14.18-Interleukin-2 fusion protein

Interventions

hu14.18-Interleukin-2 fusion protein BIOLOGICAL

Given IV

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

Disease Eval by MIBG or BM Histology (hu14.18-interleukin-2); Disease Identified by BM Immunohistochemistry Only; Disease Measurable by Standard Criteria(hu14.18-interleukin-2)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (81)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Central California

Madera, California, 93638-8762, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Sutter Cancer Center

Sacramento, California, 95816, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Stanford Comprehensive Cancer Center - Stanford

Stanford, California, 94305, United States

Location

Children's Hospital Cancer Center

Denver, Colorado, 80218-1088, United States

Location

Children's National Medical Center

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

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

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

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, 30912-3730, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62794-9620, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536-0293, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, 71315-3198, United States

Location

CancerCare of Maine at Eastern Maine Medial Center

Bangor, Maine, 04401, United States

Location

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, 02111, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Spectrum Health Hospital - Butterworth Campus

Grand Rapids, Michigan, 49503-2560, United States

Location

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, 48910, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Cancer Clinic

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109-2306, United States

Location

Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Overlook Hospital

Morristown, New Jersey, 07962, United States

Location

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

New Brunswick, New Jersey, 08903, United States

Location

University of New Mexico Cancer Research and Treatment Center

Albuquerque, New Mexico, 87131-5636, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, 28233-3549, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308-1062, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Columbus Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822-0001, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-9786, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, 29203, United States

Location

T.C. Thompson Children's Hospital

Chattanooga, Tennessee, 37403, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37901, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Texas Tech University Health Sciences Center School of Medicine - Amarillo

Amarillo, Texas, 79106, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

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

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78207, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113-1100, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Carilion Cancer Center of Western Virginia

Roanoke, Virginia, 24029, United States

Location

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, 99220-2555, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1Z2, Canada

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, N6A 4G5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

Location

Related Publications (2)

• 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.

  PMID: 20935224 RESULT

• 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.

  PMID: 20921469 RESULT

MeSH Terms

Conditions

Neuroblastoma

Interventions

lorukafusp alfa

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Paul M Sondel, MD, PhD

  University of Wisconsin, Madison

  STUDY CHAIR

• Suzanne Shusterman, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2004
• First Posted: May 19, 2004
• Study Start: August 1, 2005
• Primary Completion: February 1, 2008
• Study Completion: May 1, 2012
• Last Updated: February 12, 2015
• Results First Posted: January 16, 2014

Record last verified: 2015-01

Locations

US (69); CA (12)