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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00003750




Registration number
NCT00003750
Ethics application status
Date submitted
1/11/1999
Date registered
27/01/2003
Date last updated
8/08/2014

Titles & IDs
Public title
Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors
Scientific title
A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors
Secondary ID [1] 0 0
COG-ADVL0018
Secondary ID [2] 0 0
ADVL0018
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma (Skin) 0 0
Neuroblastoma 0 0
Sarcoma 0 0
Unspecified Childhood Solid Tumor, Protocol Specific 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - hu14.18-IL2 fusion protein

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.


Other interventions: hu14.18-IL2 fusion protein


Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Secondary outcome [1] 0 0
Assess immunological changes associated with fusion protein therapy
Timepoint [1] 0 0

Eligibility
Key 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
Minimum age
No limit
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment postcode(s) [2] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Mississippi
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
South Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Tennessee
Country [25] 0 0
United States of America
State/province [25] 0 0
Texas
Country [26] 0 0
United States of America
State/province [26] 0 0
Utah
Country [27] 0 0
United States of America
State/province [27] 0 0
Washington
Country [28] 0 0
United States of America
State/province [28] 0 0
Wisconsin
Country [29] 0 0
Canada
State/province [29] 0 0
Ontario
Country [30] 0 0
Canada
State/province [30] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00003750
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul M. Sondel, MD, PhD
Address 0 0
University of Wisconsin, Madison
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications