Biological Therapy, Sargramostim, and Isotretinoin in Treating Patients With Relapsed or Refractory Neuroblastoma
Condition: Recurrent Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial is studying how well hu14.18-interleukin-2 (IL2) fusion protein works
      when given together with sargramostim and isotretinoin in treating patients with relapsed or
      refractory neuroblastoma. Biological therapy, such as hu14.18-IL2 fusion protein, and
      sargramostim work in different ways to stimulate the immune system and stop tumor cells from
      growing. Drugs used in chemotherapy, such as isotretinoin, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving
      hu14.18-IL2 fusion protein together with sargramostim and isotretinoin may kill more tumor
      cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To evaluate the safety and tolerability of sargramostim (GM-CSF) and isotretinoin given in
      combination with hu14.18-IL-2 (hu14.18-IL2 fusion protein), as a test of feasibility for a
      future Phase III study.

      II. To evaluate the anti-tumor activity of hu14.18-IL2 given in combination with GM-CSF and
      isotretinoin in patients with recurrent or refractory neuroblastoma with disease measurable
      by standard radiographic criteria (stratum-1).

      III. To evaluate the anti-tumor activity of hu14.18-IL2 given in combination with GM-CSF and
      isotretinoin in patients with recurrent or refractory neuroblastoma evaluable only by meta
      iodo benzyl guanidine I 123 (MIBG) scintigraphy and/or bone marrow histology (stratum-2).

      SECONDARY OBJECTIVES:

      I. To describe the disease burden of stratum-2 patients by semi-quantitative assessment of
      bone marrow and MIBG scintigraphy and determine whether there is an association between lower
      disease burden and response to hu14.18-IL2.

      II. To assess molecular parameters of response (reverse-transcriptase (RT) polymerase chain
      reaction (PCR)) for patients meeting complete response (CR) criteria.

      III. To evaluate the immunologic activation induced in vivo by hu14.18-IL2. IV. To determine
      the induction of anti-hu14.18-IL2 antibody by treatment with hu14.18-IL2.

      V. To test for associations between tumor response versus immune activation and
      anti-hu14.18-IL2 activity, and between measurements of toxicity versus immune activation and
      anti-hu14.18-IL2 activity.

      OUTLINE: 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 meta iodo benzyl guanidine I 123 (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
      (PO) 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.
    

Intervention name(s): hu14.18-IL2 fusion protein; isotretinoin; sargramostim; laboratory biomarker analysis
Intervention type(s): Biological; Drug; Biological; Other
Intervention description(s): Given IV; Given PO; Given SC; Correlative studies
Other intervention name(s): EMD 273063; hu14.18-IL2; 13-CRA; Amnesteem; Cistane; Claravis; Sotret; GM-CSF; Leukine; Prokine
Intervention MeSH terms: Isotretinoin; Sargramostim
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment