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

August 6, 2014 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
      • Montreal, Quebec, Canada, H3G 1A4
        • McGill University Health Center - Montreal Children's Hospital
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94115
        • UCSF Comprehensive Cancer Center
      • Stanford, California, United States, 94305-5208
        • Stanford Cancer Center at Stanford University Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • Shands Cancer Center at the University of Florida Health Science Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • Kansas Cancer Institute at the University of Kansas Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • MBCCOP - LSU Health Sciences Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02111
        • Floating Hospital for Children
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0914
        • University of Michigan Comprehensive Cancer Center
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
      • Saint Louis, Missouri, United States, 63105
        • Washington University Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Cancer Center at Hackensack University Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Robert Wood Johnson Medical School
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU School of Medicine's Kaplan Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center at Columbia University
      • Syracuse, New York, United States, 13210
        • University Hospital at State University of New York - Upstate Medical University
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
      • Columbus, Ohio, United States, 43205-2696
        • Children's Hospital of Columbus
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73126
        • Oklahoma University Medical Center at University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97225
        • CCOP - Columbia River Oncology Program
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Hollings Cancer Center at Medical University of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38105-2794
        • St. Jude Children's Research Hospital
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center
      • San Antonio, Texas, United States, 78207
        • University of Texas Health Science Center at San Antonio
      • Temple, Texas, United States, 76508
        • CCOP - Scott and White Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Comprehensive Cancer Center
      • Marshfield, Wisconsin, United States, 54449
        • CCOP - Marshfield Clinic Research Foundation
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Biological: hu14.18-IL2 fusion protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
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 Outcome Measures

Outcome Measure
Assess immunological changes associated with fusion protein therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Paul M. Sondel, MD, PhD, University of Wisconsin, Madison

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2001

Primary Completion (Actual)

January 1, 2005

Study Completion (Actual)

September 1, 2005

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

August 8, 2014

Last Update Submitted That Met QC Criteria

August 6, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADVL0018
  • COG-ADVL0018 (Other Identifier: Children's Oncology Group)
  • CDR0000066870 (Other Identifier: Clinical Trials.gov)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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