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

Sarcoma Clinical Trial

Official title:

A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003750
• Other study ID #: ADVL0018
• Secondary ID: COG-ADVL0018CDR0
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: August 6, 2014
• Start date: October 2001
• Est. completion date: September 2005

Study information

• Verified date: August 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: September 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Biological:
• hu14.18-IL2 fusion protein

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children	Boston	Massachusetts
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida
United States	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Texas Children's Cancer Center	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Cancer Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee
United States	Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Oklahoma University Medical Center at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University Medical Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
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	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	University Hospital at State University of New York - Upstate Medical University	Syracuse	New York
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & 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) a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		No
Secondary	Assess immunological changes associated with fusion protein therapy			No