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AzTrials

Glioblastoma Multiforme (WHO Grade IV)Phase 1NCT00272870

Treatment of Newly Diagnosed Brain Tumors With Chemotherapy and Radiation Using Cells Modified for Chemoprotection and an Experimental Drug to Decrease the Tumor Cell Resistance to Chemotherapy

A Phase 1 study testing 06Benzylguanine, MGMT P140K and Meltenyi CliniMacs in people with Glioblastoma Multiforme (WHO Grade IV) and Anaplastic Astrocytoma (WHO Grade III), run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Cure rates for patients with high grade glioma remain disappointing, in part because tumor cells are often resistant to chemotherapy, and because using higher doses of chemotherapy causes damage to normal blood cells. This trial is designed to try to overcome both of these barriers. Read more about this study

Who is it for?
Ages 5 to 55 years
What is being tested?
06Benzylguanine, MGMT P140K and Meltenyi CliniMacs
Type of treatment
Medical device
How many people
1 participants
Where
1 siteUnited States
Study dates
Dec 2005to Aug 2012
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 5 to 55 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 3.1.1 Age > 5 years and < 55 years. NOTE: Subjects ages 5-30 are eligible to be treated at Cincinnati Children's Hospital Medical Center; subjects over age 30 will be treated at Ohio State University Comprehensive Cancer Center.
  • 3.1.2 Anticipated life expectancy of at least nine months 3.1.3 Karnofsky score > 50 for patients > 10 years of age, and Lansky score > 50 for patients < 10 years of age. 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.
  • 3.1.4 Patients must have one of the following newly-diagnosed central nervous system tumors, confirmed by histologic verification: Glioblastoma multiforme (WHO grade IV) OR Anaplastic astrocytoma (WHO grade III)
  • 3.1.5 Patients older than 30 years that have undergone a gross total resection and who do not have measurable disease on post operative MRI; measurable disease as assessed by post operative MRI is required on patients 30 years of age or younger.
  • 3.1.6 Neurologic deficits and corticosteroid doses must be stable or decreasing at the time of study entry.
  • 3.1.7 Adequate organ function as defined by: Serum creatinine < upper limit of normal, or GFR > 70 ml/min/1.73 m2 Total bilirubin < 2.0 mg/dl; SGPT (ALT) AND SGOT (AST) < 2.5x upper limit of normal; serum albumin > 2.0 g/dL Absolute neutrophil count > 1,000/µl, platelet count > 75,000/µl independent of transfusions
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  • 3.1.8 The patient and/or the patient's legally authorized guardian must give written informed consent according to local Institutional and/or University Human Experimentation Committee requirements.
  • 3.1.9 Women or men with reproductive potential must use effective contraception throughout the study. Effective contraception methods for women would include either an oral or transdermal contraceptive, injectable contraceptive (e.g., Depo-Provera), or contraceptive implants (e.g., intrauterine device). All males on study must agree to the use of condoms during intercourse.
  • 3.1.10 Women of reproductive potential must have a negative serum pregnancy test.

Who cannot join

  • 3.2.1 Any prior treatment with chemotherapy or radiotherapy.
  • 3.2.2 Any tumor arising in the spine or brainstem.
  • 3.2.3 Presence of metastatic disease in the spine.
  • 3.2.4 WHO grade III oligodendroglioma or oligoastrocytoma.
  • 3.2.5 Active infection at time of study entry.
  • 3.2.6 Pregnant or lactating females are excluded, because of the known teratogenic effects of alkylating agents.
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  • 3.2.7 Known HIV-positive patients. Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy and are excluded from this study. An infectious disease screen consisting of HIV I \& II Ab and NAT, HTLV I \& II Ab, RPR, Hepatitis B Surface Ag, Hepatitis B Core Ab and Hepatitis C Ab will be obtained at study entry.
  • 3.2.8 Concurrent treatment with other investigational anti-cancer agents.
  • 3.2.9 Serious illness or medical condition which would not permit the patient to be managed according to the protocol.
  • 3.2.10 Low-grade glioma (WHO Grade 1-2).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

Other trials in United States

About this study

Official title: A Pilot Study of Temozolomide and 06Benzylguanine for Treatment of Newly Diagnosed High Grade Glioma, Using Autologous Peripheral Blood Stem Cells Genetically Modified for Chemoprotection

Cure rates for patients with high grade glioma remain disappointing, in part because tumor cells are often resistant to chemotherapy, and because using higher doses of chemotherapy causes damage to normal blood cells. This trial is designed to try to overcome both of these barriers. The idea is to make tumor cells more sensitive to a chemotherapy agent, Temozolomide, by using 06Benzylguanine (06BG). In addition, patients will have a portion of their blood cells modified by the insertion of a chemotherapy resistance gene which may help protect blood cells from damage by the combination of the Temozolomide and 06BG.

Read the detailed description

The use of temozolomide (TEM) both during and after irradiation is a promising new approach for the treatment of patients with high-grade glioma. However, this treatment is limited by tumor cell resistance and therapy-related hematologic toxicity. To overcome TEM resistance, in this study we will add the chemotherapy sensitizing drug O6-Benzylguanine (BG). To overcome hematologic toxicity, patients will receive autologous hematopoietic stem cells transduced with a chemotherapy resistance gene designed to protect these cells from subsequent therapy with this drug combination.

The potential benefit of using transduced blood stem cells is the possibility for dose escalation of TEM, since hematologic toxicity has heretofore limited higher doses. Transduction will be accomplished with a retroviral vector carrying MGMTP140K, which codes for a mutated form of the resistance protein methylguanine-DNA methyltransferase (MGMT). Successful transduction of hematopoietic cells with MGMTP140K makes them resistant to the toxic effects of both TEM + BG. Repeated doses of these drugs should therefore result in an increase in the percentage of transduced (and thus protected) blood stem cells, thus reducing the likelihood of hematologic toxicity with further therapy. Accordingly, patients who are tolerating therapy well and who have laboratory evidence of chemoprotection will receive intrapatient dose escalation of TEM + BG during courses 2-6.

Eligible patients must be between 5 and 55 years of age and have newly-diagnosed high-grade glioma (anaplastic astrocytoma or glioblastoma multiforme) which cannot be completely resected. No prior therapy other than surgery is allowed, and patients must have adequate performance status and organ function as defined in the protocol.

Being tested
06Benzylguanine, MGMT P140K, Meltenyi CliniMacs
Medical subject headings
Glioblastoma, Astrocytoma, Lymphoma, Follicular

What participants receive

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

  • 06BenzylguanineDrug

    120 mg/m2/day; given Day 1-5 for up to 6 courses in Block 3

  • MGMT P140KGenetic

    Gene manipulated cells, patients are not expected to receive greater than approximately 10 x 10e6 transduced CD34+ cells/kg

  • Meltenyi CliniMacsDevice

    Device used for CD34+ cell separation of peripheral collection

What is being measured

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

  1. To assess the safety and feasibility of infusing autologous PBSC transduced with MSCV-MGMTP140K construct, using the fibronectin component CH-296 to assist gene transfer.

    Measured: 5 years

Secondary outcomes (2)

  1. Assess the efficiency of gene transfer and durability of transgene expression in this clinical setting.

    Measured: 5 years

  2. Assess the degree of chemotherapy resistance in transduced cells, and the ability to enrich the population of transduced stem cells with subsequent courses of chemotherapy.

    Measured: 5 years

Timeline

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

  1. First posted9 Jan 2006 (estimated)
  2. Study startDec 2005
  3. Primary completionDec 2008
  4. Study completionAug 2012

Why it stopped: Slow accrual; drug availability

Resources

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
Diagnosis
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00272870
Sponsor's protocol ID
CCHMCEH003
Status last verified
Aug 2012
First submitted
4 Jan 2006
Last updated
29 Aug 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 06Benzylguanine, MGMT P140K and Meltenyi CliniMacs in people with Glioblastoma Multiforme (WHO Grade IV) and Anaplastic Astrocytoma (WHO Grade III), run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

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 9 inclusion and 10 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: stopped early, as of the sponsor's last update on 29 Aug 2012. 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 stopped early (reason given: Slow accrual; drug availability). Results are not available in the source record.

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?

To assess the safety and feasibility of infusing autologous PBSC transduced with MSCV-MGMTP140K construct, using the fibronectin component CH-296 to assist gene transfer. (time frame: 5 years). 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 NCT00272870.

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 29 Aug 2012.

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