Adult Anaplastic AstrocytomaPhase 1NCT02055196

Genetically Modified Stem Cells and Irinotecan Hydrochloride in Treating Patients With Recurrent High-Grade Gliomas

A Phase 1 study testing carboxylesterase-expressing allogeneic neural stem cells, irinotecan hydrochloride and laboratory biomarker analysis in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by City of Hope Medical Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 to 64 years
Conditions the study is for: Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma
What is being tested?: carboxylesterase-expressing allogeneic neural stem cells, irinotecan hydrochloride and laboratory biomarker analysis
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: Start not givento May 2014
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 64 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

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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
There is no limit to the number of prior therapies
Patient must be able to understand and be willing to sign a written informed consent document
Patient has a prior, histopathologically-confirmed diagnosis of glioblastoma
Patient has not received any therapy for recurrent disease
INCLUSION CRITERIA FOR PROCEEDING TO TREATMENT WITH IRINOTECAN DURING CYCLE 1
A patient's daily total dose of dexamethasone must be =< 16 mg by day 3

Who cannot join

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)

Show all 12Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

City of Hope Medical Center
Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase I Study of Intracranially Administered Carboxylesterase-Expressing Neural Stem Cells in Combination With Intravenous Irinotecan in Patients With Recurrent High-Grade Gliomas

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.

Read the detailed description

PRIMARY OBJECTIVES:

To define the recommend phase II doses of intracranially administered active modified human form of carboxylesterase (hCE1m6)- neuronal stem cells (NSCs) (carboxylesterase-expressing allogeneic neural stem cells) in combination with intravenous irinotecan (irinotecan hydrochloride).

II. To determine the biologic activity of the hCE1m6-NSCs by comparing SN-38 concentrations in the brain after treatment with hCE1m6-NSCs and irinotecan compared to irinotecan alone.

SECONDARY OBJECTIVES:

To investigate the relationship between hCE1m6-NSC dose and SN-38 concentrations in brain interstitium.

II. To characterize the relationship between intracerebral and systemic concentrations of irinotecan and SN-38.

III. To assess for possible development of NSC immunogenicity after first exposure and with repeat doses of NSCs.

IV. To evaluate the intracerebral distribution of NSCs by using iron-labeling as a cellular tracker.

To describe the clinical benefit (defined as stable disease, partial response, or complete response) in patients who receive treatment with repeat cycles of NSCs and irinotecan.

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

OUTLINE: This is a dose-escalation study of carboxylesterase-expressing allogeneic neural stem cells.

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 intravenously (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.

After completion of study treatment, patients are followed up for at least 15 years.

Conditions: Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Being tested: carboxylesterase-expressing allogeneic neural stem cells, irinotecan hydrochloride, laboratory biomarker analysis
Medical subject headings: Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

carboxylesterase-expressing allogeneic neural stem cellsBiological
Also called hCE1m6-NSC
Given via intracerebral catheter
irinotecan hydrochlorideDrug
Also called Campto, Camptosar, CPT-11, irinotecan
Given IV
laboratory biomarker analysisOther
Correlative studies

Study groups in NCT02055196
Study group	Role	What they receive
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. Receives: Biological: carboxylesterase-expressing allogeneic neural stem cells; Drug: irinotecan hydrochloride; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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
Results will be summarized in an exploratory fashion using descriptive statistics and graphical methods.
Measured: Up to 15 years
NSC biodistribution in the brain via Feraheme-labeling of NSCs and MR imaging
Results will be summarized in an exploratory fashion using descriptive statistics and graphical methods.
Measured: Up to 15 years
Clinical benefit measured by tumor response
Measured: Up to 15 years
NSC persistence at autopsy
Results will be summarized in an exploratory fashion using descriptive statistics and graphical methods.
Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

?May 2014

First posted5 Feb 2014 (estimated)
Primary completionMay 2014

Why it stopped: New study written

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Adult Anaplastic AstrocytomaStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02055196
Sponsor's protocol ID: 13455
Other IDs: NCI-2014-00117, 13455, P30CA033572
Status last verified: May 2014
First submitted: 30 Jan 2014
Last updated: 2 Jun 2014
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Adult Anaplastic Astrocytoma trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Study of Intracranially Administered Carboxylesterase-Expressing Neural Stem Cells in Combination With Intravenous Irinotecan in Patients With Recurrent High-Grade Gliomas
ClinicalTrials.gov ID: NCT02055196
Acronym / sponsor ID: 13455
Conditions: Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: New study written
Enrolment: 0 participants (actual)
Lead sponsor: City of Hope Medical CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Primary completion: May 2014 (actual)
First posted: 5 Feb 2014 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To define the recommend phase II doses of intracranially administered active modified human form of carboxylesterase (hCE1m6)- neuronal stem cells (NSCs) (carboxylesterase-expressing allogeneic neural stem cells) in combination with intravenous irinotecan (irinotecan hydrochloride).

II. To determine the biologic activity of the hCE1m6-NSCs by comparing SN-38 concentrations in the brain after treatment with hCE1m6-NSCs and irinotecan compared to irinotecan alone.

SECONDARY OBJECTIVES:

To investigate the relationship between hCE1m6-NSC dose and SN-38 concentrations in brain interstitium.

II. To characterize the relationship between intracerebral and systemic concentrations of irinotecan and SN-38.

III. To assess for possible development of NSC immunogenicity after first exposure and with repeat doses of NSCs.

IV. To evaluate the intracerebral distribution of NSCs by using iron-labeling as a cellular tracker.

To describe the clinical benefit (defined as stable disease, partial response, or complete response) in patients who receive treatment with repeat cycles of NSCs and irinotecan.

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

OUTLINE: This is a dose-escalation study of carboxylesterase-expressing allogeneic neural stem cells.

After completion of study treatment, patients are followed up for at least 15 years.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (neuronal stem cells, irinotecan hydrochloride)	Experimental	Biological: carboxylesterase-expressing allogeneic neural stem cells, Drug: irinotecan hydrochloride, Other: laboratory biomarker analysisPatients 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.

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (21 listed)

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

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
carboxylesterase-expressing allogeneic neural stem cellsAlso: hCE1m6-NSCGiven via intracerebral catheter	Biological	Treatment (neuronal stem cells, irinotecan hydrochloride)
irinotecan hydrochlorideAlso: Campto, Camptosar, CPT-11, irinotecanGiven IV	Drug	Treatment (neuronal stem cells, irinotecan hydrochloride)
laboratory biomarker analysisCorrelative studies	Other	Treatment (neuronal stem cells, irinotecan hydrochloride)

Primary outcome

Incidence of dose-limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 6 weeks
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.
Incidence of all attributable toxicities, graded according to NCI CTCAE version 4.0
Time frame: Up to 15 years
Tables will be created to summarize all toxicities and side effects by dose, course, organ severity (by NCI CTCAE version 4.0), and attribution.
Biologic activity of the hCE1m6-NSCs through Cmax and AUC of irinotecan and SN-38 in dialysate and plasma
Time frame: 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
Data from patients who undergo intracerebral microdialysis will be summarized using descriptive statistics and graphical methods.

4 secondary outcomes

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
Time frame: Up to 15 years
NSC biodistribution in the brain via Feraheme-labeling of NSCs and MR imaging
Time frame: Up to 15 years
Clinical benefit measured by tumor response
Time frame: Up to 15 years
NSC persistence at autopsy
Time frame: Up to 15 years

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2014.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jana Portnow principal investigator

City of Hope Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 2 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02055196.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2014.