MedPath

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

Phase 2
Completed
Conditions
Neuroblastoma
Interventions
Biological: hu14.18-Interleukin-2 fusion protein
Registration Number
NCT00082758
Lead Sponsor
Children's Oncology Group
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
39
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Disease Eval by MIBG or BM Histology (hu14.18-interleukin-2)hu14.18-Interleukin-2 fusion proteinPatients 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
Disease Identified by BM Immunohistochemistry Onlyhu14.18-Interleukin-2 fusion proteinPatients 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
Disease Measurable by Standard Criteria(hu14.18-interleukin-2)hu14.18-Interleukin-2 fusion proteinPatients 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
Primary Outcome Measures
NameTimeMethod
Number of Responders (Response Rate)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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (81)

Childrens Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Siteman Cancer Center at Barnes-Jewish Hospital

🇺🇸

St. Louis, Missouri, United States

Geisinger Medical Center

🇺🇸

Danville, Pennsylvania, United States

Hackensack University Medical Center Cancer Center

🇺🇸

Hackensack, New Jersey, United States

Presbyterian Cancer Center at Presbyterian Hospital

🇺🇸

Charlotte, North Carolina, United States

Children's Hospital Medical Center of Akron

🇺🇸

Akron, Ohio, United States

Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

University of Mississippi Cancer Clinic

🇺🇸

Jackson, Mississippi, United States

Columbus Children's Hospital

🇺🇸

Columbus, Ohio, United States

Overlook Hospital

🇺🇸

Morristown, New Jersey, United States

Medical City Dallas Hospital

🇺🇸

Dallas, Texas, United States

Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

IWK Health Centre

🇨🇦

Halifax, Nova Scotia, Canada

Centre Hospitalier Universitaire de Quebec

🇨🇦

Quebec, Canada

Carilion Cancer Center of Western Virginia

🇺🇸

Roanoke, Virginia, United States

Children's Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

Children's Memorial Hospital - Chicago

🇺🇸

Chicago, Illinois, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Children's Hospital Central California

🇺🇸

Madera, California, United States

Stanford Comprehensive Cancer Center - Stanford

🇺🇸

Stanford, California, United States

Sacred Heart Cancer Center at Sacred Heart Hospital

🇺🇸

Pensacola, Florida, United States

MBCCOP - Medical College of Georgia Cancer Center

🇺🇸

Augusta, Georgia, United States

Kaplan Cancer Center at St. Mary's Medical Center

🇺🇸

West Palm Beach, Florida, United States

Southern Illinois University School of Medicine

🇺🇸

Springfield, Illinois, United States

University of Chicago Cancer Research Center

🇺🇸

Chicago, Illinois, United States

Tulane Cancer Center Office of Clinical Research

🇺🇸

Alexandria, Louisiana, United States

CancerCare of Maine at Eastern Maine Medial Center

🇺🇸

Bangor, Maine, United States

Spectrum Health Hospital - Butterworth Campus

🇺🇸

Grand Rapids, Michigan, United States

Breslin Cancer Center at Ingham Regional Medical Center

🇺🇸

Lansing, Michigan, United States

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

🇺🇸

New Brunswick, New Jersey, United States

Blumenthal Cancer Center at Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

T.C. Thompson Children's Hospital

🇺🇸

Chattanooga, Tennessee, United States

East Tennessee Children's Hospital

🇺🇸

Knoxville, Tennessee, United States

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

Texas Tech University Health Sciences Center School of Medicine - Amarillo

🇺🇸

Amarillo, Texas, United States

Cook Children's Medical Center - Fort Worth

🇺🇸

Fort Worth, Texas, United States

Providence Cancer Center at Sacred Heart Medical Center

🇺🇸

Spokane, Washington, United States

CancerCare Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

McMaster Children's Hospital at Hamilton Health Sciences

🇨🇦

Hamilton, Ontario, Canada

Children's Hospital of Western Ontario

🇨🇦

London, Ontario, Canada

Hopital Sainte Justine

🇨🇦

Montreal, Quebec, Canada

Montreal Children's Hospital at McGill University Health Center

🇨🇦

Montreal, Quebec, Canada

Indiana University Melvin and Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Floating Hospital for Children at Tufts - New England Medical Center

🇺🇸

Boston, Massachusetts, United States

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

🇺🇸

Boston, Massachusetts, United States

Sunrise Hospital and Medical Center

🇺🇸

Las Vegas, Nevada, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Cleveland Clinic Taussig Cancer Center

🇺🇸

Cleveland, Ohio, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

🇺🇸

Minneapolis, Minnesota, United States

University of Minnesota Cancer Center at University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

University of Texas Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

UCSF Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Primary Children's Medical Center

🇺🇸

Salt Lake City, Utah, United States

Oklahoma University Cancer Institute

🇺🇸

Oklahoma City, Oklahoma, United States

New York Medical College

🇺🇸

Valhalla, New York, United States

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

Children's & Women's Hospital of British Columbia

🇨🇦

Vancouver, British Columbia, Canada

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

🇺🇸

Birmingham, Alabama, United States

Children's Hospital Cancer Center

🇺🇸

Denver, Colorado, United States

Alberta Children's Hospital

🇨🇦

Calgary, Alberta, Canada

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

🇺🇸

Tampa, Florida, United States

Midwest Children's Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

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

🇺🇸

Dallas, Texas, United States

Children's Hospital of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Palmetto Health South Carolina Cancer Center

🇺🇸

Columbia, South Carolina, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Virginia Commonwealth University Massey Cancer Center

🇺🇸

Richmond, Virginia, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

🇺🇸

Madison, Wisconsin, United States

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

University of Florida Shands Cancer Center

🇺🇸

Gainesville, Florida, United States

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

🇺🇸

Chapel Hill, North Carolina, United States

Sutter Cancer Center

🇺🇸

Sacramento, California, United States

Markey Cancer Center at University of Kentucky Chandler Medical Center

🇺🇸

Lexington, Kentucky, United States

Kosair Children's Hospital

🇺🇸

Louisville, Kentucky, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

University of New Mexico Cancer Research and Treatment Center

🇺🇸

Albuquerque, New Mexico, United States

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