ANBL1021: Feasibility/Phase II Study of hu14.18-IL2 Immunocytokine + GM-CSF and Isotretinoin in Patients with Relapsed or Refractory Neuroblastoma
What is the purpose of this study?
This phase II trial is studying how well biological therapy works when given together with sargramostim and isotretinoin in treating patients with relapsed or refractory neuroblastoma.
Who can participate?
Ages 1 through 30.
- Patients must have had histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines at the time of initial diagnosis
- Patients must have resistant/refractory or recurrent neuroblastoma
- Tumor imaging and bone marrow evaluation for histologic analysis of marrow tumor cell quantity must be obtained within 3 weeks (21 days) prior to enrollment onto study and patients must have one of the following:
- Measurable tumor on MRI, CT scan, or x-ray defined as minimum of 20 mm in at least one dimension
- For patients who are in first response (i.e., those patients with persistent sites of tumor after frontline therapy, but who have never relapsed), a biopsy of a lesion or bone marrow must demonstrate viable neuroblastoma following completion of therapy
- If the lesion was irradiated, the biopsy must be done at least 4 weeks after radiation is completed
- Meta-iodobenzyl guanidine I 123 (MIBG) scan with positive uptake at minimum of one sitMeta-iodobenzyl guanidine I 123 (MIBG) scan with positive uptake at minimum of one site
- For patients in first response, a biopsy of site must demonstrate viable tumor
- If lesion was radiated, biopsy must be done at least 4 weeks after radiation completed
- Bone marrow with tumor cells seen on routine morphology (not by neuron specific enolase [NSE] staining only) of bilateral aspirate and/or biopsy on one bone marrow sample
- No patients with symptomatic pleural effusions or ascites (requiring constant or intermittent drainage)
- Patients with a history of CNS disease must have no clinical or radiological evidence of CNS disease at the time of protocol enrollment
- Performance status (PS) 0-2
- Karnofsky PS 50-100% for patients > 16 years of age and Lansky PS 50-100% for patients ≤ 16 years of age
- Patients must have a life expectancy of ≥ 8 weeks
- Absolute phagocyte count (APC) ≥ 1,000/μL
- Platelet count ≥ 20,000/μL*
- Hemoglobin ≥ 8 g/dL*
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 month to < 6 months of age)
- 0.5 mg/dL (6 months to < 1 years of age)
- 0.6 mg/dL (1 to < 2 years of age)
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
- Not pregnant or nursing
- Negative pregnancy test
- Patients of childbearing potential must agree to use an effective birth control method
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT ≤ 1.5 times ULN
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 55% by gated radionuclide study
- QTC interval < 450 msec
- Patients must have normal respiratory function defined as no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% on room air
- If pulmonary function tests (PFTs) are performed, the FEV1/FVC must be greater than 60%
- Patients with seizure disorders may be enrolled if on anti-convulsants and well-controlled
- CNS toxicity ≤ grade 2
- Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance are not eligible
- Patients with prior history of ventilator support related to lung injury (lung injury such as pneumonia, hemorrhagic pneumonitis, capillary leakage) are excluded
- Patients with significant serious intercurrent illnesses (any other ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and which is expected to interfere with the action of hu14.18-IL2 or to significantly increase the severity of the toxicities experienced from hu14.18-IL2 treatment are not eligible.
NOTE: *Transfusions are permitted if known history of bone marrow involvement with tumor.
What is involved?
This is a multicenter study. Patients are stratified according to measurable disease (disease measurable by standard radiographic criteria [stratum-1] vs disease evaluable only by 123I-MIBG and/or bone marrow histology [stratum-2]).
Patients receive sargramostim subcutaneously (SC [preferred]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin orally twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve stable disease (SD) after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment.
Patients may undergo blood and bone marrow sample collection periodically for correlative studies.
After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then yearly for 2 years.
Who should I contact for more information?
Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Where can I find additional information?