Clinical trial NCT00003750: Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 28
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein
Secondary outcomes:
measure: Assess immunological changes associated with fusion protein therapy
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Cancer Center at the University of Florida Health Science Center
state: Florida
city: Atlanta
country: United States
facility: AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: Kansas Cancer Institute at the University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Floating Hospital for Children
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: Hackensack
country: United States
facility: Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Syracuse
country: United States
facility: University Hospital at State University of New York - Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center at University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Texas Children's Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center - Montreal Children's Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
Study officials:
affiliation: University of Wisconsin, Madison
name: Paul M. Sondel, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.