Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors

NCT00003750 | Completed Phase 1 DMC

• 3 other identifiers: ADVL0018COG-ADVL0018CDR0000066870
• Study Type: interventional
• Target: 28
• Locations: 3 countries
• Sites: 59

Brief Summary

RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors.

Conditions

Melanoma (Skin); Neuroblastoma; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

metastatic osteosarcoma; recurrent neuroblastoma; recurrent osteosarcoma; recurrent melanoma; unspecified childhood solid tumor, protocol specific; metastatic childhood soft tissue sarcoma; recurrent childhood soft tissue sarcoma

Outcome Measures

Primary Outcomes (1)

• Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein

  Determine the MTD of hu14.18-IL2 fusion protein and determine the pharmacokinetics of the fusion protein when given as I.V. injections

Secondary Outcomes (1)

• Assess immunological changes associated with fusion protein therapy

Study Arms (1)

DG2 positive relapsed or refractory solid tumors

EXPERIMENTAL

The initial hu14.18-IL2 fusion protein (FP) dose will be 2 mg/m2 given intravenously over 4 hours, daily for 3 days. Five separate dose levels are scheduled: 2 mg/m²/dose (IV over 4 hours) x 3 days, 4 mg/m²/dose (IV over 4 hours) x 3 days, 6 mg/m²/dose (IV over 4 hours) x 3 days, 8 mg/m²/dose (IV over 4 hours) x 3 days, 10 mg/m²/dose (IV over 4 hours) x 3 days.

Biological: hu14.18-IL2 fusion protein

Interventions

hu14.18-IL2 fusion protein BIOLOGICAL

DG2 positive relapsed or refractory solid tumors

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 or melanoma at original diagnosis * Refractory to chemotherapy or recurrence after prior multiagent chemotherapy * Measurable or evaluable (detectable by bone scan) metastatic disease OR * No evidence of disease if complete response to prior surgical resection, radiotherapy, and/or chemotherapy OR * Histologically confirmed tumor expressing GD2 antigen at original diagnosis or relapse * Refractory to standard treatment * Measurable or evaluable disease by clinical assessments or laboratory markers OR * No evidence of disease after prior surgical resection of metastatic, recurrent disease * Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy allowed * Soft tissue sarcoma allowed * No primary CNS tumors * Prior CNS metastases allowed, provided: * Disease previously treated * Disease clinically stable for 4 weeks before study * At least 4 weeks since prior steroids for CNS metastases * No clinically detectable pleural effusions or ascites PATIENT CHARACTERISTICS: Age: * 21 and under Performance status: * Karnofsky 60-100% for children over age 10 * Lansky 60-100% for children age 10 and under Life expectancy: * At least 12 weeks Hematopoietic: * Absolute neutrophil count greater than 1,000/mm\^3 * Platelet count at least 75,000/mm\^3 (transfusion allowed) * Hemoglobin at least 9.0 g/dL (transfusion allowed) Hepatic: * Bilirubin less than 1.5 mg/dL * ALT or AST no greater than 2.5 times normal * Hepatitis B surface antigen negative Renal: * Creatinine no greater than 1.5 mg/dL OR * Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min Cardiovascular: * Shortening fraction at least 27% by echocardiogram OR * Ejection fraction more than 50% by MUGA scan * No congestive heart failure * No uncontrolled cardiac rhythm disturbance Pulmonary: * FEV\_1 and FVC more than 60% of predicted OR * No dyspnea at rest * No exercise intolerance * Oxygen saturation more than 94% by pulse oximetry on room air Neurologic: * No seizure disorders requiring antiseizure medications * No significant neurologic deficit or grade 2 or greater objective peripheral neuropathy Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * No significant concurrent illnesses unrelated to cancer or its treatment * No significant psychiatric disabilities * No uncontrolled active infections * No uncontrolled active peptic ulcer PRIOR CONCURRENT THERAPY: Biologic therapy: * At least 1 week since prior growth factors * At least 1 week since prior immunomodulatory therapy * Prior monoclonal antibodies allowed if no detectable antibody to hu14.18 * Prior autologous bone marrow transplantation (BMT) or stem cell transplantation (SCT) allowed * Prior autologous BMT or SCT with monoclonal antibody-purged specimens allowed * No concurrent growth factors * No concurrent interferon Chemotherapy: * See Disease Characteristics * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or melphalan) * No concurrent palliative chemotherapy Endocrine therapy: * See Disease Characteristics * At least 2 weeks since prior glucocorticoids, except for life-threatening symptoms * No concurrent corticosteroids * No concurrent glucocorticoids, except for life-threatening symptoms Radiotherapy: * See Disease Characteristics * At least 3 weeks since prior radiotherapy * No concurrent palliative radiotherapy Surgery: * See Disease Characteristics * At least 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy) * No prior organ allografts * No concurrent palliative surgery Other: * Recovered from prior therapy * At least 1 week since prior tretinoin * At least 3 weeks since prior immunosuppressive therapy * No other concurrent immunosuppressive 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 (59)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095-1781, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, 94305-5208, United States

Location

Children's National Medical Center

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

Location

Shands Cancer Center at the University of Florida Health Science Center

Gainesville, Florida, 32610-0296, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus

Atlanta, Georgia, 30342, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Kansas Cancer Institute at the University of Kansas Medical Center

Kansas City, Kansas, 66160-7357, United States

Location

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Floating Hospital for Children

Boston, Massachusetts, 02111, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0914, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Washington University Medical Center

St Louis, Missouri, 63105, United States

Location

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, 10032, United States

Location

University Hospital at State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Columbus

Columbus, Ohio, 43205-2696, United States

Location

Oklahoma University Medical Center at University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73126, United States

Location

CCOP - Columbia River Oncology Program

Portland, Oregon, 97225, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425-0721, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105-2794, United States

Location

Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center

Nashville, Tennessee, 37232-6838, United States

Location

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

Dallas, Texas, 75390-9063, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030-2399, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78207, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, 54449, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

McGill University Health Center - Montreal Children's Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Osenga KL, Hank JA, Albertini MR, Gan J, Sternberg AG, Eickhoff J, Seeger RC, Matthay KK, Reynolds CP, Twist C, Krailo M, Adamson PC, Reisfeld RA, Gillies SD, Sondel PM; Children's Oncology Group. A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res. 2006 Mar 15;12(6):1750-9. doi: 10.1158/1078-0432.CCR-05-2000.

  PMID: 16551859 RESULT

MeSH Terms

Conditions

Melanoma; Neuroblastoma; Sarcoma; Osteosarcoma

Interventions

lorukafusp alfa

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Study Officials

• Paul M. Sondel, MD, PhD

  University of Wisconsin, Madison

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: October 1, 2001
• Primary Completion: January 1, 2005
• Study Completion: September 1, 2005
• Last Updated: August 8, 2014

Record last verified: 2014-08

Locations

AU (2); CA (3); US (54)