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

Neuroblastoma Clinical Trial

Official title:

A Phase II Study Of hu14.18-IL2 In Children With Recurrent Or Refractory Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00082758
• Other study ID #: ANBL0322
• Secondary ID: CDR0000360723COG
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2004
• Last updated: January 27, 2015
• Start date: August 2005
• Est. completion date: May 2012

Study information

• Verified date: January 2015
• 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 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.

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 information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: May 2012
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed neuroblastoma

• Relapsed or refractory to conventional therapy

• Measurable or evaluable disease documented by 1 of the following criteria:

• Clinical

• Radiographic

• Histologic

• MIBG (meta-iodobenzylguanidine) scanning

• Immunocytochemistry

• No symptomatic pleural effusions or ascites requiring constant or intermittent drainage

• No clinical or radiological evidence of central nervous system (CNS) disease

PATIENT CHARACTERISTICS:

Age

• 21 and under

Performance status

• Karnofsky 50-100% (> 16 years of age)

• Lansky 50-100% (= 16 years of age)

Life expectancy

• At least 8 weeks

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3

• Platelet count = 75,000/mm^3*

• Must not be refractory to platelet transfusions

• Hemoglobin = 9.0 g/dL* NOTE: *Transfusion allowed if patient is known to have a history of bone marrow involvement with tumor

Hepatic

• Alanine transaminase (ALT) < 2.5 times upper limit of normal (ULN)

• Bilirubin = 1.5 times ULN

• Hepatitis B surface antigen negative

Renal

• Creatinine adjusted according to age as follows:

• No greater than 0.4 mg/dL (= 5 months)

• No greater than 0.5 mg/dL (6 months -11 months)

• No greater than 0.6 mg/dL (1 year-23 months)

• No greater than 0.8 mg/dL (2 years-5 years)

• No greater than 1.0 mg/dL (6 years-9 years)

• No greater than 1.2 mg/dL (10 years-12 years)

• No greater than 1.4 mg/dL (13 years and over [female])

• No greater than 1.5 mg/dL (13 years to 15 years [male])

• No greater than 1.7 mg/dL (16 years and over [male]) OR

• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Cardiovascular

• Shortening fraction = 27% by echocardiogram OR

• Ejection fraction = 50% by Multi Gated Acquisition Scan (MUGA)

• No symptomatic congestive heart failure

• No uncontrolled cardiac rhythm disturbance

Pulmonary

• Pulse oximetry > 94% on room air

• Forced vital capacity (FVC) > 80%

• Forced expiratory volume (FEV_1) > 80%

• No abnormal respiratory function

• No dyspnea at rest

• No exercise intolerance

• No prior history of ventilator support related to lung injury (e.g., pneumonia, hemorrhagic pneumonitis, or capillary leakage)

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• HIV negative

• No active uncontrolled infection

• No active uncontrolled peptic ulcer

• No objective peripheral neuropathy = grade 2

• No significant psychiatric disabilities

• No seizure disorders requiring antiseizure medications

• No other concurrent significant illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior immunotherapy

• Prior in vivo monoclonal antibodies for biologic therapy or tumor imaging allowed provided there is documented absence of detectable antibody to hu14.18 by serology

• More than 28 days since prior autologous stem cell transplantation

• Prior autologous marrow or stem cell infusion using monoclonal antibody-purged specimens allowed

• More than 1 week since prior growth factors

• At least 7 days since prior nonmyelosuppressive biologic agents

• No prior allogeneic bone marrow or stem cell transplantation

• No concurrent immunomodulating agents

• No concurrent growth factors

Chemotherapy

• More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered

• No concurrent anticancer chemotherapy

Endocrine therapy

• No concurrent corticosteroids except 100 mg or less of hydrocortisone (or equivalent) as premedication for blood transfusion or treatment for transfusion reaction

• No other use of systemic steroids

Radiotherapy

• Recovered from prior radiotherapy

• At least 2 weeks since prior local palliative radiotherapy (small port)

• At least 6 months since prior craniospinal radiotherapy

• At least 6 months since prior total body irradiation

• At least 6 months since prior radiotherapy to = 50% of the pelvis

• At least 6 weeks since other prior substantial bone marrow radiotherapy

• Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable or evaluable lesion is not irradiated

Surgery

• More than 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy)

• No prior organ allografts

Other

• No concurrent immunosuppressive drugs

• No other concurrent myelosuppressive antineoplastic drugs

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• hu14.18-Interleukin-2 fusion protein
Given IV

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
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	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children at Tufts - New England Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	T.C. Thompson Children's Hospital	Chattanooga	Tennessee
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina
United States	Columbus Children's Hospital	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Children's Hospital Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center	Lebanon	New Hampshire
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
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	Overlook Hospital	Morristown	New Jersey
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Carilion Cancer Center of Western Virginia	Roanoke	Virginia
United States	Sutter Cancer Center	Sacramento	California
United States	Primary Children's Medical Center	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	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri
United States	Stanford Comprehensive Cancer Center - Stanford	Stanford	California
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Delgado DC, Hank JA, Kolesar J, Lorentzen D, Gan J, Seo S, Kim K, Shusterman S, Gillies SD, Reisfeld RA, Yang R, Gadbaw B, DeSantes KB, London WB, Seeger RC, Maris JM, Sondel PM. Genotypes of NK cell KIR receptors, their ligands, and Fc? receptors in the — View Citation

Shusterman S, London WB, Gillies SD, et al.: Anti-neuroblastoma activity of hu14.18-IL2 against minimal residual disease in a Children's Oncology Group (COG) phase II study. [Abstract] J Clin Oncol 26 (Suppl 15): A-3002, 2008.

Shusterman S, London WB, Gillies SD, Hank JA, Voss SD, Seeger RC, Reynolds CP, Kimball J, Albertini MR, Wagner B, Gan J, Eickhoff J, DeSantes KB, Cohn SL, Hecht T, Gadbaw B, Reisfeld RA, Maris JM, Sondel PM. Antitumor activity of hu14.18-IL2 in patients w — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Responders (Response Rate)	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.	Up to 30 weeks	No