NCT02444546

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2015

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 1, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 14, 2015

Completed
1 month until next milestone

Study Start

First participant enrolled

June 21, 2015

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 13, 2018

Completed
4.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 21, 2022

Completed
Last Updated

April 24, 2023

Status Verified

April 1, 2023

Enrollment Period

3.1 years

First QC Date

May 1, 2015

Last Update Submit

April 21, 2023

Conditions

Childhood AstrocytomaChildhood Atypical Teratoid/Rhabdoid TumorDiffuse Intrinsic Pontine GliomaGliomaRecurrent Childhood Anaplastic OligodendrogliomaRecurrent Childhood Brain NeoplasmRecurrent Childhood GlioblastomaRecurrent Childhood MedulloblastomaRecurrent Primitive Neuroectodermal TumorRefractory Brain Neoplasm

Outcome Measures

Primary Outcomes (1)

  • MTD, based on the incidence of dose-limiting toxicity (DLT) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0

    MTD is the highest safely tolerated dose level where 1 of 6 patients experience DLT with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT.

    Up to 84 days

Secondary Outcomes (8)

  • Adverse event profile

    Up to 5 years

  • Objective responses

    Up to 5 years

  • Overall survival

    Up to 5 years

  • Time to progression

    Will be summarized descriptively.

  • Time to treatment failure

    Up to 5 years

  • +3 more secondary outcomes

Other Outcomes (2)

  • Immunologic parameters

    Up to 5 years

  • Reovirus immune status

    Up to 5 years

Study Arms (1)

Treatment (sargramostim, wild-type reovirus)

EXPERIMENTAL

Patients receive sargramostim SC daily on days 1 and 2 and wild-type reovirus 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.

Other: Laboratory Biomarker AnalysisBiological: SargramostimBiological: Wild-type Reovirus

Interventions

Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (sargramostim, wild-type reovirus)
SargramostimBIOLOGICAL

Given SC

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin
Treatment (sargramostim, wild-type reovirus)
Wild-type ReovirusBIOLOGICAL

Given IV

Also known as: Reolysin
Treatment (sargramostim, wild-type reovirus)

Eligibility Criteria

Age10 Years - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Histological confirmation of a high grade (grade 3 or 4) primary brain tumor either classified as a glioma (including astrocytoma, anaplastic oligodendroglioma and glioblastoma multiforme), medulloblastoma, atypical teratoid/rhabdoid tumor (AT/RT) or primitive neuroectodermal tumor (PNET)
  • Note: Patients with diffuse intrinsic pontine glioma (DIPG) are exempt from this confirmation of tumor if characteristic radiologic findings are noted on magnetic resonance imaging (MRI)
  • Patients must have no known curative therapy available
  • Evidence of tumor progression by MRI scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan
  • Measurable disease: measurable by gadolinium MRI scan
  • Absolute neutrophil count (ANC) \>= 750 /uL obtained =\< 7 days prior to registration
  • Absolute lymphocyte count (ALC) \>= 250/uL obtained =\< 7 days prior to registration
  • Platelet count (PLT) \>= 75,000 /uL without transfusions obtained =\< 7 days prior to registration
  • Hemoglobin \>= 7.0 gm/dL obtained =\< 7 days prior to registration
  • Total bilirubin =\< 1.5 times upper limit of institutional normal (ULN) for age obtained =\< 7 days prior to registration
  • Aspartate transaminase (AST) =\< 3 times ULN for age obtained =\< 7 days prior to registration
  • Serum albumin \>= 2 g/dL
  • Creatinine =\< 1.5 times ULN for age OR a creatinine clearance or glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2; obtained =\< 7 days prior to registration
  • Karnofsky or Lansky performance status (PS): performance status of \>= 50 assessed within two weeks prior to registration; neurological deficits in patients must have been relatively stable for a minimum of 1 week prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Ability to understand and the willingness to provide written informed assent or consent
  • +8 more criteria

You may not qualify if:

  • Fetal and newborn toxicity: any of the following
  • Pregnant women
  • Nursing women
  • Males or post-menarchal females who are unwilling to employ adequate contraception throughout the duration of the study and for at least 4 weeks after treatment has ended
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection, including localized infections
  • Symptomatic congestive heart failure
  • Unstable angina pectoris or cardiac arrhythmia
  • Any psychiatric illness/social situations that would limit compliance with study requirements
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Known prior history of tuberculosis or positive purified protein derivative (PPD) test result
  • Known prior history of human immunodeficiency virus (HIV)
  • Administration of live vaccines =\< 14 days prior to registration; note: patients may not receive any viral immunizations during the study and for 28 days after the last dose of Reolysin
  • Prior history of any viral-based therapy
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration \[FDA\]-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm:
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Rhabdoid TumorDiffuse Intrinsic Pontine GliomaGliomaOligodendrogliomaAstrocytomaMedulloblastomaNeuroectodermal Tumors, PrimitiveBrain Neoplasms

Interventions

sargramostimColony-Stimulating Factorsreolysin

Condition Hierarchy (Ancestors)

Neoplasms, Complex and MixedNeoplasms by Histologic TypeNeoplasmsNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueBrain Stem NeoplasmsInfratentorial NeoplasmsCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

GlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Study Officials

  • Richard Bram

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 1, 2015

First Posted

May 14, 2015

Study Start

June 21, 2015

Primary Completion

July 13, 2018

Study Completion

November 21, 2022

Last Updated

April 24, 2023

Record last verified: 2023-04

Locations

US(1)