hu14.18-Interleukin-2 Fusion Protein in Treating Young Patients With Recurrent or Refractory Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: hu14.18-Interleukin-2 fusion protein
Intervention description: Given IV
Intervention MeSH terms: Interleukin-2; Denileukin diftitox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: recurrent neuroblastoma

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.
    

Eligibility criteria:

        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