NCT02055196

Brief Summary

This phase I trial studies the side effects and best dose of genetically modified stem cells when given together with irinotecan hydrochloride in treating patients with recurrent high-grade gliomas. Irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Placing a gene that has been created in the laboratory into neural stem cells and injecting it into the brain may help irinotecan hydrochloride kill more tumor cells once it reaches the brain.

Trial Health

35
At Risk

Trial Health Score

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

Geographic Reach
1 country

1 active site

Status
withdrawn

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

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 30, 2014

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 5, 2014

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Last Updated

June 2, 2014

Status Verified

May 1, 2014

First QC Date

January 30, 2014

Last Update Submit

May 30, 2014

Conditions

Adult Anaplastic AstrocytomaAdult Anaplastic OligodendrogliomaAdult Giant Cell GlioblastomaAdult GlioblastomaAdult GliosarcomaRecurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (3)

  • Incidence of dose-limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Tables will be created to summarize all toxicities and side effects by dose, course, organ severity (by NCI CTCAE version 4.0), and attribution. Rates and associated 95% Clopper Pearson confidence limits will be estimated for the DLT and clinical benefit at the MTD for cohort 1 and cohort 2 and in combination if the results are similar.

    6 weeks

  • Incidence of all attributable toxicities, graded according to NCI CTCAE version 4.0

    Tables will be created to summarize all toxicities and side effects by dose, course, organ severity (by NCI CTCAE version 4.0), and attribution.

    Up to 15 years

  • Biologic activity of the hCE1m6-NSCs through Cmax and AUC of irinotecan and SN-38 in dialysate and plasma

    Data from patients who undergo intracerebral microdialysis will be summarized using descriptive statistics and graphical methods.

    Prior to the start of the irinotecan infusion and at 90 minutes (just prior to the end of the infusion), and then at 30 minutes, 1, 2, 4, 8, 24, and 48 hours after the end of the infusion on day 3 of week 1

Secondary Outcomes (4)

  • Incidence of immunogenicity measured by the development of T cell responses and antibodies against the NSCs using TcR Vβ spectratyping, CD 107 degranulation assays, and flow cytometry

    Up to 15 years

  • NSC biodistribution in the brain via Feraheme-labeling of NSCs and MR imaging

    Up to 15 years

  • Clinical benefit measured by tumor response

    Up to 15 years

  • NSC persistence at autopsy

    Up to 15 years

Study Arms (1)

Treatment (neuronal stem cells, irinotecan hydrochloride)

EXPERIMENTAL

Patients receive carboxylesterase-expressing allogeneic neural stem cells via intracerebral catheter on day 1 of week 1; weeks 1 and 3, weeks 1, 2, and 3; or weeks 1, 2, 3, and 4. Patients also receive irinotecan hydrochloride IV over 90 minutes on day 3 of week 1; weeks 1 and 3, weeks 1, 2, and 3; or weeks 1, 2, 3, and 4. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Biological: carboxylesterase-expressing allogeneic neural stem cellsDrug: irinotecan hydrochlorideOther: laboratory biomarker analysis

Interventions

carboxylesterase-expressing allogeneic neural stem cellsBIOLOGICAL

Given via intracerebral catheter

Also known as: hCE1m6-NSC
Treatment (neuronal stem cells, irinotecan hydrochloride)
irinotecan hydrochlorideDRUG

Given IV

Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E
Treatment (neuronal stem cells, irinotecan hydrochloride)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (neuronal stem cells, irinotecan hydrochloride)

Eligibility Criteria

Age18 Years - 64 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Patient has a prior, histologically-confirmed, diagnosis of a grade III or IV glioma (including glioblastoma, 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)
  • 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
  • PROTOCOL-SPECIFIC CRITERIA
  • 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
  • Patients who will undergo tumor resection must have residual enhancing tumor (i.e. a gross total resection is not anticipated)
  • Based on the neurosurgeon's judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
  • Absolute neutrophil count (ANC) of \>= 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
  • +5 more criteria

You may not qualify if:

  • Patient is homozygous or heterozygous for the UDP glycosyltransferase 1 family, polypeptide A1\*28 allele (UGT 1A1\*28) allele and/or has Gilbert's disease
  • Patient must not be taking any cytochrome P450 3A4 (CYP3A4) hepatic enzyme-inducing anticonvulsants (phenytoin, fosphenytoin \[Cerebyx\], carbamazepine, phenobarbital, primidone, oxcarbazepine) or other moderate to strong CYP3A4 inhibitors or inducers for at least 2 weeks prior to start of study treatment
  • Patient has anti-human leukocyte antigen (HLA) antibodies specific for HLA antigens expressed by the F3.CD.CE 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, and at least 2 weeks from taking the last dose of a targeted agent and the start of study treatment, with the exception of bevacizumab, where a wash out period of at least 4 weeks is required before starting study treatment
  • Patient is taking flucytosine
  • Patient is unable to undergo a magnetic resonance imaging (MRI)
  • Patient has chronic or active viral infections of the central nervous system (CNS) or an uncontrolled illness
  • Patient may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is participating in this study
  • A patient with another active malignancy is ineligible for this study
  • Non-compliance

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

AstrocytomaOligodendrogliomaGlioblastomaGliosarcomaBrain Neoplasms

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

GliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic Compounds

Study Officials

  • Jana Portnow

    City of Hope Medical Center

    PRINCIPAL INVESTIGATOR
0

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

January 30, 2014

First Posted

February 5, 2014

Primary Completion

May 1, 2014

Last Updated

June 2, 2014

Record last verified: 2014-05

Locations

US(1)