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

NCT ID: NCT00003750

Last Updated: 2014-08-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-10-31

Study Completion Date

2005-09-30

Brief Summary

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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.

Detailed Description

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OBJECTIVES:

* Determine the maximum tolerated dose of hu14.18-interleukin-2 fusion protein in children with refractory or recurrent neuroblastoma or other GD2-positive tumors.
* Determine the toxicity and pharmacokinetics of the fusion protein in these patients.
* Determine the effect of the fusion protein on systemic immune modulation in these patients.
* Quantitate the antifusion protein antibodies in patients treated with fusion protein.
* Evaluate antitumor responses resulting from this fusion protein regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive hu14.18-interleukin-2 (hu14.18-IL2) fusion protein IV over 4 hours once daily on days 1-3. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of hu14.18-IL2 fusion protein until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 2 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 1 year.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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DG2 positive relapsed or refractory solid tumors

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.

Group Type EXPERIMENTAL

hu14.18-IL2 fusion protein

Intervention Type BIOLOGICAL

Interventions

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hu14.18-IL2 fusion protein

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul M. Sondel, MD, PhD

Role: STUDY_CHAIR

University of Wisconsin, Madison

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Shands Cancer Center at the University of Florida Health Science Center

Gainesville, Florida, United States

Site Status

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

Atlanta, Georgia, United States

Site Status

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Kansas Cancer Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Floating Hospital for Children

Boston, Massachusetts, United States

Site Status

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

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

Washington University Medical Center

St Louis, Missouri, United States

Site Status

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, United States

Site Status

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

Syracuse, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Columbus

Columbus, Ohio, United States

Site Status

Oklahoma University Medical Center at University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status

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

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Texas Children's Cancer Center

Houston, Texas, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

McGill University Health Center - Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Australia Canada

References

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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.

Reference Type RESULT
PMID: 16551859 (View on PubMed)

Other Identifiers

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COG-ADVL0018

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000066870

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL0018

Identifier Type: -

Identifier Source: org_study_id

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