ClinicalTrials.gg
CompletedNCT02444546Updated Apr 24, 2023

Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors

A Phase 1 interventional study of Laboratory Biomarker Analysis and Sargramostim in Childhood Astrocytoma, Childhood Atypical Teratoid/Rhabdoid Tumor and Diffuse Intrinsic Pontine Glioma, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 10 Years to 21 Years. Per ClinicalTrials.gov, last updated 2023-04-24.

Sponsored by Mayo Clinic · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
6
Allocation
Not applicable
Ages
10 Years to 21 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

In context

Rhabdoid Tumor

115 studies on the registry are indexed under Rhabdoid Tumor; 23 are open to participants now.

This study's enrollment of 6 is below the median of 28 across 98 interventional studies indexed under Rhabdoid Tumor.

Browse Rhabdoid Tumor studies →

Lead sponsor

Mayo Clinic is the lead sponsor of 3,269 studies on the registry; 672 are open to participants now.

Of its 452 completed or terminated interventional studies of FDA-regulated products, 321 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
10 Years to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 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 by gadolinium MRI scan
  • (ANC) >= 750 /uL obtained =\< 7 days prior to registration
  • Absolute lymphocyte count (ALC) >= 250/uL obtained =\< 7 days prior to registration
  • count (PLT) >= 75,000 /uL without transfusions obtained =\< 7 days prior to registration
  • >= 7.0 gm/dL obtained =\< 7 days prior to registration
  • Total =\< 1.5 times upper limit of institutional normal () for age obtained =\< 7 days prior to registration
  • (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 or (GFR) >= 70 mL/min/1.73 m\^2; obtained =\< 7 days prior to registration
  • 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
  • Willing to return to enrolling institution for follow-up
  • : patients must be receiving a stable or decreasing dose of dexamethasone for at least 1 week prior to start of therapy AND dexamethasone dose must be =\< 0.1 mg/kg/day AND =\< a total daily dose of 4 mg/day
  • If patient has a clinically indicated surgery or at any time during treatment with Reolysin, a tissue sample will be collected for correlative research purposes
  • Patient willing to provide mandatory blood samples for correlative research purposes; the inability to provide a blood sample or the lack of an available blood sample does not make the patient ineligible
  • Negative urine or serum pregnancy test done =\< 7 days prior to registration for females who are post-menarchal
  • Patient agrees to use an acceptable form of during the study and for up to 28 days after the last dose of Reolysin if patient or female partner is post-menarche; acceptable methods include 1) a double barrier method, such as condom and spermicide; 2) hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e., 'mini-pill'); 3) intrauterine device (non-progesterone T); 4) surgical methods such as a bilateral tubal ligation or a vasectomy; 5) abstinence
  • Must be able to avoid direct contact with pregnant women, infants \< 3 months of age and immunocompromised individuals while on study and for >= 3 weeks following the last dose of study agent administration; direct contact is defined as household contact, i.e., anyone living with the patient
  • >= 3 months

Exclusion criteria

Exclusion Criteria:

  • Fetal and newborn toxicity: any of the following

    • Pregnant women
    • Nursing women
    • Males or post-menarchal females who are unwilling to employ adequate 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 (HIV)
  • Administration of =\< 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 (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:

    • Chemotherapy =\< 3 weeks of registration
    • Nitrosoureas or mitomycin C =\< 6 weeks of registration
    • Small molecule cell cycle inhibitors =\< 2 weeks prior to registration
    • Immunotherapy =\< 6 weeks prior to registration
    • Monoclonal antibodies =\< 3 half-lives prior to registration
    • Radiation therapy

      • Last fraction of craniospinal irradiation or total body irradiation =\< 3 months prior to registration or last fraction of focal irradiation to symptomatic sites =\< 4 weeks prior to registration
    • Growth factors

      • Colony forming growth factors \< 2 weeks prior to registration (i.e., filgrastim, sargramostim, erythropoietin)
      • Neulasta \< 2 weeks prior to registration
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
Terms in these criteria, in plain language(18)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
6 participants (actual)

Study arms

  • Experimental
    Treatment (sargramostim, wild-type reovirus)

    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 Analysis · Biological: Sargramostim · Biological: Wild-type Reovirus

Interventions

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • BiologicalSargramostim

    Given SC

    Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

  • Given IV

    Also known as: Reolysin

06

What researchers measure

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.

    Time frame: Up to 84 days

Secondary outcomes

  1. Adverse event profile

    The number and severity of adverse events (overall, by dose level, by treatment received) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.

    Time frame: Up to 5 years

  2. Objective responses

    Objective responses will be summarized by descriptive summary statistics delineating complete and partial responses and stable and progressive disease.

    Time frame: Up to 5 years

  3. Overall survival

    Will be summarized descriptively. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and relevant confidence intervals.

    Time frame: Up to 5 years

  4. Time to progression

    Up to 5 years

    Time frame: Will be summarized descriptively.

  5. Time to treatment failure

    Will be summarized descriptively. Time to treatment failure is defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.

    Time frame: Up to 5 years

  6. Time until any treatment-related toxicity

    Will be summarized descriptively.

    Time frame: Up to 5 years

  7. Time until treatment-related grade 3+ toxicity

    Will be summarized descriptively.

    Time frame: Up to 5 years

  8. Toxicity profile, assessed by CTCAE v4.0

    Toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Overall toxicity incidence and toxicity profiles by dose level, patient, and treatment will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of the analysis.

    Time frame: Up to 5 years

Other outcomes

  1. Immunologic parameters

    For each of the immunologic parameters, a time series plot will be constructed. A grid reflecting the percent change from pre-treatment levels will be constructed. This grid will be analyzed to determine if the changes seen in each immunologic parameter differ between patients who response and those which do not respond.

    Time frame: Up to 5 years

  2. Reovirus immune status

    The reovirus immune status will be correlated with objective response to analyze if the status is predictive of sargramostim plus wild-type reovirus therapy.

    Time frame: Up to 5 years

07

Study locations

1 site
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 24, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02444546
Lead sponsor
Mayo Clinic
Responsible party
Sponsor
First posted
May 14, 2015
Start date
Jun 21, 2015
Primary completion
Jul 13, 2018
Completion
Nov 21, 2022
Last update
Apr 24, 2023

Study contacts

Richard Bram
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Pelareorep

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