Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors
Condition: Childhood Astrocytoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Childhood Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor; Refractory Brain Neoplasm
MeSH terms: Neoplasms; Glioblastoma; Glioma; Brain Neoplasms; Astrocytoma; Medulloblastoma; Oligodendroglioma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Diffuse Intrinsic Pontine Glioma; Rhabdoid Tumor; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and the best dose of wild-type reovirus (viral
      therapy) when given with sargramostim in treating younger patients with high grade brain
      tumors that have come back or that have not responded to standard therapy. A virus, called
      wild-type reovirus, which has been changed in a certain way, may be able to kill tumor cells
      without damaging normal cells. Sargramostim may increase the production of blood cells and
      may promote the tumor cell killing effects of wild-type reovirus. Giving wild-type reovirus
      together with sargramostim may kill more tumor cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To define the maximum tolerated dose (MTD) and describe the toxicities of wild-type
      reovirus (Reolysin) when given once a day for three days following two days of treatment with
      sargramostim (GM-CSF).

      SECONDARY OBJECTIVES:

      I. To assess the safety, tolerability and adverse events in the patient population.

      II. To assess the median overall survival time in this patient population. III. To assess the
      median progression free survival time in this patient population.

      TERTIARY OBJECTIVES:

      I. To determine whether there is a correlation between antibody responsiveness to the virus
      and a positive tumor response to Reolysin in patients who receive the virus following
      treatment with GM-CSF.

      II. To determine whether there is a correlation between an increased number of circulating
      monocytes and a positive tumor response to Reolysin in patients who receive the virus
      following treatment with GM-CSF.

      III. To explore the possible predictive value of monocyte numbers in response to Reolysin +
      GM-CSF therapy.

      OUTLINE: This is a dose-escalation study of wild-type reovirus.

      Patients receive sargramostim subcutaneously (SC) daily on days 1 and 2 and wild-type
      reovirus intravenously (IV) over 60 minutes on days 3-5. Treatment repeats every 28 days for
      12 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 1 year,
      every 4 months for 1 year, every 6 months for 1 year, and then annually for up to 2 years.
    

Intervention name(s): Laboratory Biomarker Analysis; Sargramostim; Wild-type Reovirus
Intervention type(s): Other; Biological; Biological
Intervention description(s): Correlative studies; Given SC; Given IV
Other intervention name(s): 23-L-Leucinecolony-Stimulating Factor 2; DRG-0012; Leukine; Prokine; rhu GM-CFS; Sagramostim; Sargramostatin; Reolysin
Intervention MeSH terms: Sargramostim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment