NCT01334515

Biological Therapy, Sargramostim, and Isotretinoin in Treating Patients With Relapsed or Refractory Neuroblastoma

Feasibility/Phase II Study of hu14.18-IL2 Immunocytokine + GM-CSF and Isotretinoin in Patients With Relapsed or Refractory Neuroblastoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Recurrent Neuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	hu14.18-IL2 fusion protein	Given IV
DRUG	isotretinoin	Given PO
BIOLOGICAL	sargramostim	Given SC
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2011-09-01
• Primary completion: 2013-12-31
• Completion: 2019-09-30
• First posted: 2011-04-13
• Last updated: 2019-10-21
• Results posted: 2015-02-20

Locations

76 sites across 2 countries: United States, Canada