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

Phase 2
21 Years
Not Enrolling

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Trial Information

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


- 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

- 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 scanning and/or bone marrow histology vs disease identified and quantified by bone
marrow immunohistochemistry).

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.

Inclusion Criteria


- Histologically confirmed neuroblastoma

- Relapsed or refractory to conventional therapy

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

- Clinical

- Radiographic

- Histologic

- MIBG scanning

- Immunocytochemistry

- No symptomatic pleural effusions or ascites requiring constant or intermittent

- No clinical or radiological evidence of CNS disease



- 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


- 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


- ALT < 2.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- Hepatitis B surface antigen negative


- 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


- Shortening fraction ≥ 27% by echocardiogram OR

- Ejection fraction ≥ 50% by MUGA

- No symptomatic congestive heart failure

- No uncontrolled cardiac rhythm disturbance


- Pulse oximetry > 94% on room air

- FVC > 80%

- 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)


- 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


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


- 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


- 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


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

- No prior organ allografts


- No concurrent immunosuppressive drugs

- No other concurrent myelosuppressive antineoplastic drugs

Type of Study:


Study Design:

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

Outcome Measure:

Best overall response (complete response, very good partial response, or partial response)

Outcome Description:

Proportion of responders within each stratum. Patients deemed inevaluable for response will have available response data tabulated and reported descriptively, but will not be counted in the target accrual for response for each strata. Stratum 03 patients will not be included in the statistical analysis to determine activity of hu14.18-IL2, since there is not sufficient data to support the significance of immunocytologic responses. Such responses will be tabulated and reported

Outcome Time Frame:

Up to 30 weeks

Safety Issue:


Principal Investigator

Paul M Sondel, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Wisconsin, Madison


United States: Federal Government

Study ID:




Start Date:

August 2005

Completion Date:

May 2012

Related Keywords:

  • Neuroblastoma
  • recurrent neuroblastoma
  • Neuroblastoma



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