Genetically Modified Neural Stem Cells, Flucytosine, and Leucovorin for Treating Patients With Recurrent High-Grade Gliomas

Sponsor
City of Hope Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02015819
Collaborator
National Cancer Institute (NCI) (NIH)
16
1
1
36
0.4

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and determines the best dose of genetically modified neural stem cells and flucytosine when given together with leucovorin for treating patients with recurrent high-grade gliomas. Neural stem cells can travel to sites of tumor in the brain. The neural stem cells that are being used in this study were genetically modified express the enzyme cytosine deaminase (CD), which converts the prodrug flucytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Leucovorin may help 5-FU kill more tumor cells. The CD-expressing neural stem cells are administered directly into the brain. After giving the neural stem cells a few days to spread out and migrate to tumor cells, research participants take a 7 day course of oral 5-FC. (Depending on when a research participant enters the study, they may also be given leucovorin to take with the 5-FC.) When the 5-FC crosses into brain, the neural stem cells convert it into 5-FU, which diffuses out of the neural stem cells to preferentially kill rapidly dividing tumor cells while minimizing toxicity to healthy tissues. A Rickham catheter, placed at the time of surgery, will be used to administer additional doses of NSCs every two weeks, followed each time by a 7 day course of oral 5-FC (and possibly leucovorin). This neural stem cell-based anti-cancer strategy may be an effective treatment for high-grade gliomas.

Funding Source - FDA OOPD

Condition or Disease Intervention/Treatment Phase
  • Biological: E. coli CD-expressing genetically modified neural stem cells
  • Drug: flucytosine
  • Drug: leucovorin calcium
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Phase 1

Detailed Description

PRIMARY OBJECTIVES:
  1. To define the phase II recommended dose of intracerebrally administered cytosine deaminase (CD)-expressing neural stem cells (NSCs) in combination with oral 5-fluorocytosine (FC) (flucytosine) and leucovorin.

  2. To determine the feasibility of treating study patients with more than 1 dose of NSCs followed by 7-day courses of 5-FC and leucovorin.

SECONDARY OBJECTIVES:
  1. To assess for possible development of NSC immunogenicity (anti-NSC T cell and/or antibody response) with repeat doses of NSCs.

  2. To characterize the relationship between intracerebral and systemic concentrations of 5-FC and 5-FU at the maximum tolerated dose/maximum feasible dose level.

  3. To describe the clinical benefit (defined as stable disease, partial response, or complete response) of this treatment regimen.

  4. To determine, at time of autopsy, the fate of the NSCs.

OUTLINE: This is dose-escalation study of CD-expressing genetically modified neural stem cells and flucytosine.

Patients receive CD-expressing neural stem cells intracranially (IC) on days 1 and 15 and flucytosine orally (PO) every 6 hours on days 4-10 and 18-24. Depending on when a subject enters the study, they may also be given leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days, 3 months, 6 months, 1 year, and then annually thereafter.

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells in Combination With Oral 5-Fluorocytosine and Leucovorin for the Treatment of Recurrent High-Grade Gliomas
Actual Study Start Date :
Oct 7, 2014
Actual Primary Completion Date :
Oct 7, 2017
Actual Study Completion Date :
Oct 7, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (neural stem cells, flucytosine, leucovorin)

Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Depending on when a subject enters the study, they may also be given leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dose escalation used the following dose levels: Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis

Biological: E. coli CD-expressing genetically modified neural stem cells
Given intracranially
Other Names:
  • HB1.F3.CD neural stem cells
  • Drug: flucytosine
    Given orally
    Other Names:
  • 5-FC
  • 5-fluorocytosine
  • Ro 2-9915
  • Drug: leucovorin calcium
    Given orally
    Other Names:
  • CF
  • CFR
  • LV
  • Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD) [Day 28 of course 1]

      Number of DLTs per dose level and the MTD/MFD.

    2. Number of Participants With Mechanical Issues With Repeat Administrations of NSCs Via Rickham [28 days after last infusion of NSCs, up to 6 months total]

      Number of participants with mechanical issues with repeat administrations of NSCs via Rickham.

    Secondary Outcome Measures

    1. Number of Participants Developing Antibodies Against NSCs [While receiving treatment, up to 6 months.]

      Development of a antibody response to the NSCs will be evaluated by flow cytometry. Data from assessing for possible development of NSC immunogenicity with repeat exposure will be presented in an exploratory fashion using descriptive statistics.

    2. Average Steady State Levels of 5-FC and 5-FU in the Brain [Following the first dose of 5-FC, samples were collected every hour for 24 hours and then every 3 hours thereafter until the end of the 7-day course of 5-FC or until the microdialysis catheter stopped functioning.]

      Pharmacokinetic (PK) data from the patients who undergo intracerebral microdialysis (dose level 4) will be summarized using descriptive statistics. All summaries will be exploratory in spirit.

    3. Average Steady State Levels of 5-FC Concentrations in Plasma [Samples were obtained prior to the first dose of 5-FC then every 30 minutes for 3 hours, additional samples at 4 and 6 hours after the morning doses on days 4, 5. On days 6, 7, 8 blood samples were collected just before morning dose and 90 minutes later]

      PK data from the patients who undergo intracerebral microdialysis (dose level 4) will be summarized using descriptive statistics.

    4. Comparison of 5-FC in the Brain to 5-FC in the Plasma [The ratio of average brain interstitial 5-FC and 5-FU concentrations to average plasma steady-state levels was calculated using all measured data.]

      PK data from the patients who undergo intracerebral microdialysis (dose level 4) will be summarized using the mean ratio of average brain interstitial 5-FC concentrations to the average steady-state plasma levels.

    5. Summary of Tumor Response Using the Response Assessment in Neuro-Oncology (RANO) Criteria [Up to 3 years post NSC infusion]

      Per RANO criteria: Complete Response (CR): Complete disappearance of all enhancing disease that is sustained for at least 4 weeks, stable or improved non-enhancing FLAIR/T2 lesions, no new lesions, off corticosteroids, and neurologically stable or improved. Partial Response (PR): >= 50% decrease of all measurable enhancing lesions, sustained or at least 4 weeks, no progression of non-measurable disease, stable or improved non-enhancing FLAIR/T2 lesions, non new lesions, corticosteroid dose stable or reduced, and neurologically stable or improved. Stable Disease (SD): Dose not qualify for CR, PR, or PD, stable non-enhancing FLAIR/T2 lesions, stable or reduced corticosteroids, clinically stable. Progressive Disease (PD): >=25% increase in enhancing lesion despite stable or increasing steroid dose, increase (significant) in non-enhancing T2/FLAIR lesions that is not attributable to other non-tumor causes, any new lesions, clinical deterioration

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patient has had a prior, histologically-confirmed, diagnosis of a grade III or IV glioma (including glioblastoma, anaplastic oligodendroglioma, or anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma), or has a prior, histologically-confirmed, diagnosis of a grade II glioma and now has radiographic findings consistent with a high-grade glioma (grade III or IV)

    • Imaging studies show evidence of recurrent, supratentorial tumor(s). The presence of infratentorial tumor is allowed as long as the patient also has supratentorial disease that is amenable to resection or biopsy.

    • Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide

    • Patient has a Karnofsky performance status of >= 70%

    • Patient has a life expectancy of >= 3 months

    • Female patients of childbearing potential and sexually-active male patients must agree to use an effective method of contraception while participating in this study; women of childbearing potential must have a negative pregnancy test =< 2 weeks prior to registration

    • The patient must be in need of a craniotomy for tumor resection or a stereotactic brain biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy

    • Based on the neurosurgeon's judgement, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles

    • Absolute neutrophil count (ANC) >= 1500 cells/mm^3

    • Platelet count >= 100,000 cells/mm^3

    • Total bilirubin =< 2.0 mg/dl

    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 4 times the institutional upper limit of normal

    • Serum creatinine =< the institutional upper limit of normal

    • There is no limit to the number of prior therapies

    • All subjects must have the ability to understand and the willingness to sign a written informed consent

    Exclusion Criteria:
    • Patient has anti-human leukocyte antigen (HLA) antibodies specific for HLA antigens expressed by the NSCs

    • Patient has not recovered from any toxicity of prior therapies; an interval of

    • At least 6 weeks must have elapsed since taking a nitrosourea-containing chemotherapy regimen

    • At least 4 weeks since completing a non-nitrosourea-containing cytotoxic chemotherapy regimen (except temozolomide: only an interval of 23 days is required from the last dose administered when patient has been recently treated with the standard temozolomide regimen of daily for 5 days, repeated every 28 days)

    • At least 2 weeks from taking the last dose of targeted agent

    • At least 4 weeks from the last dose of bevacizumab

    • Patient is unable to undergo a magnetic resonance imaging (MRI)

    • Patient is allergic to 5-FC, leucovorin, or 5-FU

    • Patient has chronic or active viral infections of the central nervous system (CNS)

    • Patient has a coagulopathy or bleeding disorder

    • Patient has an uncontrolled illness including ongoing or active infection

    • Patient is receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy

    • Patient has had prior therapy with neural stem cells

    • Patient is pregnant or breast feeding; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is participating in this study

    • Patient has another active malignancy

    • Non-compliance; a patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Medical Center Duarte California United States 91010

    Sponsors and Collaborators

    • City of Hope Medical Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Jana Portnow, City of Hope Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT02015819
    Other Study ID Numbers:
    • 13401
    • NCI-2013-02346
    • 13401
    • FD-R-004816
    First Posted:
    Dec 19, 2013
    Last Update Posted:
    Oct 20, 2021
    Last Verified:
    Sep 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. They will also be given leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED 3 3 3 7
    COMPLETED 3 3 3 6
    NOT COMPLETED 0 0 0 1

    Baseline Characteristics

    Arm/Group Title Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis Total
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Total of all reporting groups
    Overall Participants 3 3 3 7 16
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    59
    40
    57
    58
    57
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    0
    0%
    1
    33.3%
    0
    0%
    3
    18.8%
    Male
    1
    33.3%
    3
    100%
    2
    66.7%
    7
    100%
    13
    81.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    2
    66.7%
    2
    28.6%
    4
    25%
    Not Hispanic or Latino
    3
    100%
    3
    100%
    1
    33.3%
    5
    71.4%
    12
    75%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    6.3%
    White
    2
    66.7%
    2
    66.7%
    3
    100%
    7
    100%
    14
    87.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    3
    100%
    7
    100%
    16
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD)
    Description Number of DLTs per dose level and the MTD/MFD.
    Time Frame Day 28 of course 1

    Outcome Measure Data

    Analysis Population Description
    1 participant in dose level 4 was unevaluable and had to be replaced after receiving the first dose of CD-NSCs due to the tip of the Rickham catheter migrating into the lateral ventricle.
    Arm/Group Title Dose Level 1: (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2: (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 3 3 3 6
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Dose Level 1: (NSC 5x10^7 and 5-FC 37.5 mg/kg), Dose Level 2: (NSC 1x10^8 and 5-FC 37.5 mg/kg), Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg), Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg + Leucovorin + Microdialysis
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis MFD was determined to be 1.5x10^8 in combination with oral 5-FC 37.5 mg/kg and leucovorin 25 mg every 6 hours for 7 days.
    2. Primary Outcome
    Title Number of Participants With Mechanical Issues With Repeat Administrations of NSCs Via Rickham
    Description Number of participants with mechanical issues with repeat administrations of NSCs via Rickham.
    Time Frame 28 days after last infusion of NSCs, up to 6 months total

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 3 3 3 7
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Number of Participants Developing Antibodies Against NSCs
    Description Development of a antibody response to the NSCs will be evaluated by flow cytometry. Data from assessing for possible development of NSC immunogenicity with repeat exposure will be presented in an exploratory fashion using descriptive statistics.
    Time Frame While receiving treatment, up to 6 months.

    Outcome Measure Data

    Analysis Population Description
    2 participants in dose level 4 were not assessed in this analysis because one participant only received one dose of CD-NSCs and the other we were unable to obtain post second CD-NSC dose serum sample to analyze.
    Arm/Group Title Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 3 3 3 5
    Count of Participants [Participants]
    0
    0%
    2
    66.7%
    0
    0%
    1
    14.3%
    4. Secondary Outcome
    Title Average Steady State Levels of 5-FC and 5-FU in the Brain
    Description Pharmacokinetic (PK) data from the patients who undergo intracerebral microdialysis (dose level 4) will be summarized using descriptive statistics. All summaries will be exploratory in spirit.
    Time Frame Following the first dose of 5-FC, samples were collected every hour for 24 hours and then every 3 hours thereafter until the end of the 7-day course of 5-FC or until the microdialysis catheter stopped functioning.

    Outcome Measure Data

    Analysis Population Description
    Only participants in dose level 4 received intracerebral microdialysis and are included in this analysis
    Arm/Group Title Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. They will also be given leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 7
    average steady state levels of 5-FC in the brain
    213
    (58)
    average steady state levels of 5-FU in the brain
    0.03
    (0.01)
    5. Secondary Outcome
    Title Average Steady State Levels of 5-FC Concentrations in Plasma
    Description PK data from the patients who undergo intracerebral microdialysis (dose level 4) will be summarized using descriptive statistics.
    Time Frame Samples were obtained prior to the first dose of 5-FC then every 30 minutes for 3 hours, additional samples at 4 and 6 hours after the morning doses on days 4, 5. On days 6, 7, 8 blood samples were collected just before morning dose and 90 minutes later

    Outcome Measure Data

    Analysis Population Description
    Only participants in dose level 4 received intracerebral microdialysis and are included in this analysis
    Arm/Group Title Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. They will also be given leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 7
    Mean (Standard Error) [┬Ámol/L]
    748
    (218)
    6. Secondary Outcome
    Title Comparison of 5-FC in the Brain to 5-FC in the Plasma
    Description PK data from the patients who undergo intracerebral microdialysis (dose level 4) will be summarized using the mean ratio of average brain interstitial 5-FC concentrations to the average steady-state plasma levels.
    Time Frame The ratio of average brain interstitial 5-FC and 5-FU concentrations to average plasma steady-state levels was calculated using all measured data.

    Outcome Measure Data

    Analysis Population Description
    Only participants in dose level 4 received intracerebral microdialysis and are included in this analysis
    Arm/Group Title Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. They will also be given leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 7
    Mean (Standard Error) [ratio]
    29
    (21)
    7. Secondary Outcome
    Title Summary of Tumor Response Using the Response Assessment in Neuro-Oncology (RANO) Criteria
    Description Per RANO criteria: Complete Response (CR): Complete disappearance of all enhancing disease that is sustained for at least 4 weeks, stable or improved non-enhancing FLAIR/T2 lesions, no new lesions, off corticosteroids, and neurologically stable or improved. Partial Response (PR): >= 50% decrease of all measurable enhancing lesions, sustained or at least 4 weeks, no progression of non-measurable disease, stable or improved non-enhancing FLAIR/T2 lesions, non new lesions, corticosteroid dose stable or reduced, and neurologically stable or improved. Stable Disease (SD): Dose not qualify for CR, PR, or PD, stable non-enhancing FLAIR/T2 lesions, stable or reduced corticosteroids, clinically stable. Progressive Disease (PD): >=25% increase in enhancing lesion despite stable or increasing steroid dose, increase (significant) in non-enhancing T2/FLAIR lesions that is not attributable to other non-tumor causes, any new lesions, clinical deterioration
    Time Frame Up to 3 years post NSC infusion

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 3 3 3 7
    Stable Disease
    2
    66.7%
    0
    0%
    0
    0%
    1
    14.3%
    Progressive Disease
    1
    33.3%
    3
    100%
    3
    100%
    4
    57.1%
    Ineligible for Disease Response
    0
    0%
    0
    0%
    0
    0%
    2
    28.6%

    Adverse Events

    Time Frame During and after treatment, up to 20 months
    Adverse Event Reporting Description
    Arm/Group Title Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Arm/Group Description Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CD-expressing neural stem cells intracranially on days 1 and 15. Flucytosine is taken orally every 6 hours on days 4-10 and 18-24. They will also be given leucovorin orally every 6 hours on days 4-10 and 18-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    All Cause Mortality
    Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 3/3 (100%) 7/7 (100%)
    Serious Adverse Events
    Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 4/7 (57.1%)
    General disorders
    Death 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/7 (14.3%)
    Fever 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Infections and infestations
    Skin infection 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Brain abscess 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Wound infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Musculoskeletal and connective tissue disorders
    Muscle weakness left-sided 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Pain in extremity 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Nervous system disorders
    Seizure 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Intracranial hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Psychiatric disorders
    Confusion 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Vascular disorders
    Hypertension 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Thromboembolic event 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Other (Not Including Serious) Adverse Events
    Dose Level 1 (NSC 5x10^7 and 5-FC 37.5 mg/kg) Dose Level 2 (NSC 1x10^8 and 5-FC 37.5 mg/kg) Dose Level 3 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) Dose Level 4 (NSC 1.5x10^8 and 5-FC 37.5 mg/kg) + Leucovorin + Microdialysis
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 3/3 (100%) 7/7 (100%)
    Blood and lymphatic system disorders
    Anemia 2/3 (66.7%) 0/3 (0%) 2/3 (66.7%) 6/7 (85.7%)
    Cardiac disorders
    Sinus bradycardia 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 4/7 (57.1%)
    Sinus tachycardia 2/3 (66.7%) 2/3 (66.7%) 1/3 (33.3%) 4/7 (57.1%)
    Premature ventricular contractions 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    tachypnea 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Endocrine disorders
    Cushingoid 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Eye disorders
    Blurred vision 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 0/7 (0%)
    Dry eye 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/7 (14.3%)
    Eye pain 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Floaters 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/3 (0%) 2/3 (66.7%) 2/3 (66.7%) 2/7 (28.6%)
    Abdominal pain 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/7 (28.6%)
    Bloating 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Constipation 0/3 (0%) 1/3 (33.3%) 2/3 (66.7%) 5/7 (71.4%)
    Diarrhea 1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 3/7 (42.9%)
    Dry mouth 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Flatulence 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Gastrointestinal pain 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Hemorrhoids 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Nausea 1/3 (33.3%) 3/3 (100%) 3/3 (100%) 3/7 (42.9%)
    Oral pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Vomiting 1/3 (33.3%) 3/3 (100%) 1/3 (33.3%) 1/7 (14.3%)
    Ulceration on Tongue 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    mouth sores 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    General disorders
    Chills 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/7 (0%)
    Edema face 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Fatigue 3/3 (100%) 3/3 (100%) 1/3 (33.3%) 4/7 (57.1%)
    Fever 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Gait disturbance 2/3 (66.7%) 1/3 (33.3%) 2/3 (66.7%) 5/7 (71.4%)
    Pain 1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 6/7 (85.7%)
    Edema limbs 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Localized edema 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Infections and infestations
    Upper respiratory infection 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Mucosal infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Injury, poisoning and procedural complications
    Bruising 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 2/7 (28.6%)
    Fall 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 3/7 (42.9%)
    numbness at surgical site 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    swelling, right side of forehead 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Alanine aminotransferase increased 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Alkaline phosphatase increased 0/3 (0%) 0/3 (0%) 0/3 (0%) 3/7 (42.9%)
    Aspartate aminotransferase increased 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Blood bilirubin increased 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Cholesterol high 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    INR increased 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Lymphocyte count decreased 2/3 (66.7%) 1/3 (33.3%) 2/3 (66.7%) 6/7 (85.7%)
    Platelet count decreased 2/3 (66.7%) 1/3 (33.3%) 2/3 (66.7%) 7/7 (100%)
    Weight gain 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 1/7 (14.3%)
    Weight loss 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    White blood cell decreased 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Hemoglobin increased 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Metabolism and nutrition disorders
    Anorexia 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 3/7 (42.9%)
    Dehydration 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Hyperglycemia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Hypermagnesemia 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 1/7 (14.3%)
    Hypernatremia 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/7 (14.3%)
    Hypertriglyceridemia 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Hypoalbuminemia 2/3 (66.7%) 1/3 (33.3%) 2/3 (66.7%) 5/7 (71.4%)
    Hypocalcemia 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 2/7 (28.6%)
    Hypoglycemia 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Hypokalemia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Hyponatremia 2/3 (66.7%) 1/3 (33.3%) 3/3 (100%) 3/7 (42.9%)
    Hypophosphatemia 1/3 (33.3%) 1/3 (33.3%) 2/3 (66.7%) 6/7 (85.7%)
    Obesity 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Increased appetite 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Bone pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Kyphosis 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Neck pain 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Pain in extremity 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 3/7 (42.9%)
    Buttock pain 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Joint range of motion decreased 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Generalized muscle weakness 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 2/7 (28.6%)
    Muscle weakness lower limb 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 3/7 (42.9%)
    Muscle weakness left-sided 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 3/7 (42.9%)
    Muscle weakness right-sided 2/3 (66.7%) 0/3 (0%) 2/3 (66.7%) 1/7 (14.3%)
    Joint range of motion decreased cervical spine 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/7 (14.3%)
    Muscle weakness upper limb 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/7 (14.3%)
    Nervous system disorders
    Ataxia 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 3/7 (42.9%)
    Cerebrospinal fluid leakage 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Cognitive disturbance 0/3 (0%) 1/3 (33.3%) 3/3 (100%) 5/7 (71.4%)
    Concentration impairment 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Dizziness 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Dysarthria 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 0/7 (0%)
    Dysphasia 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 3/7 (42.9%)
    Headache 3/3 (100%) 3/3 (100%) 3/3 (100%) 7/7 (100%)
    Hypersomnia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/7 (28.6%)
    Lethargy 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 3/7 (42.9%)
    Memory impairment 1/3 (33.3%) 2/3 (66.7%) 2/3 (66.7%) 4/7 (57.1%)
    Paresthesia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Peripheral sensory neuropathy 3/3 (100%) 0/3 (0%) 1/3 (33.3%) 2/7 (28.6%)
    Seizure 2/3 (66.7%) 2/3 (66.7%) 1/3 (33.3%) 0/7 (0%)
    Somnolence 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 3/7 (42.9%)
    Spasticity 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Tremor 2/3 (66.7%) 0/3 (0%) 1/3 (33.3%) 2/7 (28.6%)
    Facial muscle weakness 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Facial nerve disorder 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Left-sided balance/coordination problems 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    aphasia 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    hygroma 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    tightness/swelling at right side of brain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Psychiatric disorders
    Agitation 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Anxiety 0/3 (0%) 1/3 (33.3%) 3/3 (100%) 3/7 (42.9%)
    Confusion 2/3 (66.7%) 1/3 (33.3%) 2/3 (66.7%) 4/7 (57.1%)
    Depression 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    Insomnia 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/7 (14.3%)
    Restlessness 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/7 (28.6%)
    Emotional lability 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/7 (0%)
    MOOD CHANGES 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    frustration 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    impulsive 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Renal and urinary disorders
    Proteinuria 0/3 (0%) 0/3 (0%) 0/3 (0%) 3/7 (42.9%)
    Urinary frequency 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Urinary incontinence 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Urinary retention 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 2/7 (28.6%)
    Dyspnea 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/7 (14.3%)
    Hiccups 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 1/7 (14.3%)
    Lung congestion 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Tachypnea 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    chest congestion 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Skin and subcutaneous tissue disorders
    Dry skin 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Pruritus 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 0/7 (0%)
    Rash acneiform 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Rash maculo-papular 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 0/7 (0%)
    Skin ulceration 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Scalp pain 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/7 (0%)
    Skin sore 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    blisters 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    excoriation / rash at coccyx 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)
    Vascular disorders
    Hematoma 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/7 (0%)
    Hypertension 3/3 (100%) 3/3 (100%) 2/3 (66.7%) 6/7 (85.7%)
    Hypotension 3/3 (100%) 0/3 (0%) 2/3 (66.7%) 2/7 (28.6%)
    Phlebitis 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/7 (14.3%)
    Thromboembolic event 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/7 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Jana Portnow
    Organization City of Hope Medical Center
    Phone 6262189200
    Email jportnow@coh.org
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT02015819
    Other Study ID Numbers:
    • 13401
    • NCI-2013-02346
    • 13401
    • FD-R-004816
    First Posted:
    Dec 19, 2013
    Last Update Posted:
    Oct 20, 2021
    Last Verified:
    Sep 1, 2021