Brain and Central Nervous System TumorsNCT00253487
Combination Chemotherapy and Radiation Therapy in Treating Younger Patients Who Are Undergoing an Autologous Stem Cell Transplant for Newly Diagnosed Gliomas
A study testing O6-benzylguanine, busulfan and temozolomide in people with Brain and Central Nervous System Tumors, run by Children's Hospital Medical Center, Cincinnati.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, busulfan, and O6-benzylguanine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 5 to 55 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- O6-benzylguanine, busulfan and temozolomide
- Type of treatment
- Surgery or procedure
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Aug 2005to Aug 2012
- Phase
- Interventional
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed high-grade glioma of 1 of the following types:
- Glioblastoma multiforme
- WHO grade IV disease
- Anaplastic astrocytoma
- WHO grade III disease
- No low-grade disease (i.e., WHO grade I-II disease)
- No WHO grade III oligodendroglioma or oligoastrocytoma
- Patients > 30 years of age who have undergone a gross total resection and have nonmeasurable disease as seen on postoperative MRI are eligible
- Measurable disease, as assessed by postoperative MRI, is required in patients ≤ 30 years of age
- No tumor arising in the spine or brainstem
- No metastatic disease in the spine
PATIENT CHARACTERISTICS:
Age
- 5 to 55
Performance status
- Karnofsky 50-100% (for patients 11-30 years of age) OR
- Lansky 50-100% (for patients 5-10 years of age)
Life expectancy
- At least 9 months
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 75,000/mm^3 (transfusion independent)
Hepatic
- Bilirubin ≤ 2.0 mg/dL
- ALT and AST ≤ 2.5 times upper limit of normal
- Albumin ≥ 2.0 g/dL
- Hepatitis B surface antigen and core antibody negative
- Hepatitis C antibody negative
Renal
- Creatinine normal OR
- Glomerular filtration rate ≥ 70 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Neurologic deficits must be stable or decreasing
- No active infection
- HIV negative
- No other serious illness or medical condition that would preclude study participation
PRIOR CONCURRENT THERAPY:
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Concurrent corticosteroids allowed provided dose is stable or decreasing
Radiotherapy
- No prior radiotherapy
Surgery
- See Disease Characteristics
Other
- No other concurrent investigational anticancer agents
About this study
Official title: A Pilot Study of Temozolomide and O-Benzylguanine for Treatment of High-Grade Glioma, Using Autologous Peripheral Blood Stem Cells Genetically Modified for Chemoprotection
RATIONALE: Drugs used in chemotherapy, such as temozolomide, busulfan, and O6-benzylguanine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. O6-benzylguanine may also help temozolomide work better by making tumor cells more sensitive to the drug. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy with a peripheral stem cell transplant or bone marrow transplant, using stem cells from the patient that are genetically-modified in the laboratory to protect them from the side effects of chemotherapy, may allow more chemotherapy to be given so that more tumor cells are killed. Giving combination chemotherapy and radiation therapy together with a peripheral stem cell transplant or bone marrow transplant may kill more tumor cells.
PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating younger patients who are undergoing an autologous stem cell transplant for newly diagnosed gliomas.
Read the detailed description
OBJECTIVES:
Primary
- Determine the safety and feasibility of a conditioning regimen comprising temozolomide, radiotherapy, and busulfan followed by an infusion of autologous stem cells genetically modified with the MGMT gene and temozolomide and O6-benzylguanine in younger patients with newly diagnosed high-grade gliomas.
Secondary
- Determine the tolerability of intrapatient dose escalation of temozolomide, in terms of transgene expression, in patients treated with this regimen.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is a pilot study.
- Surgery: Patients undergo biopsy or surgical debulking of the tumor. Two to six weeks later, patients proceed to stem cell mobilization and apheresis.
- Autologous stem cell mobilization and apheresis: Patients receive filgrastim (G-CSF) subcutaneously or IV once daily for at least 4 days before apheresis and continuing until apheresis is complete. Patients undergo apheresis for up to 4 consecutive days until a target number of 5 X 10^6 CD34-positive peripheral blood stem cells (PBSCs) are collected. Patients with insufficient numbers of PBSCs either undergo bone marrow harvest to collect a sufficient number of cells or are removed from the study. The cells are selected for CD34-positive cells which are cryopreserved for later use. Patients then proceed to chemoradiotherapy.
- Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42 and undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four to eight weeks later, patients proceed to the low-intensity, nonmyeloablative conditioning regimen.
- Autologous PBSC or bone marrow transduction: Peripheral blood or bone marrow CD34-positive stem cells are transduced with the MGMT gene on day -4.
- Low-intensity, nonmyeloablative conditioning regimen: Patients receive busulfan IV over 2 hours on days -3 and -2. Patients then proceed to autologous PBSC or bone marrow infusion.
- Autologous PBSC or bone marrow infusion: Patients undergo autologous stem cell infusion using transduced PBSCs or bone marrow on day 0. Three to six weeks later, patients proceed to chemotherapy.
- Chemotherapy: Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide once daily on days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to O6-benzylguanine may receive temozolomide alone. Patients not experiencing dose-limiting toxicity and who have at least 5% transduced neutrophils by peripheral blood analysis after course 1 receive escalating doses (intrapatient) of temozolomide during courses 2-6. Some patients undergo second-look surgery after the first course of chemotherapy.
After completion of study therapy, patients are followed monthly for 3 months, every 3 months for 3 years, every 6 months for 4 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 1-2 years.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- O6-benzylguanine, busulfan, temozolomide, adjuvant therapy, autologous bone marrow transplantation
- Keywords
- adult glioblastoma, adult anaplastic astrocytoma, childhood high-grade cerebral astrocytoma, adult giant cell glioblastoma, adult gliosarcoma
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Astrocytoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
O6-benzylguanineDrug
busulfanDrug
temozolomideDrug
adjuvant therapyProcedure or surgery
autologous bone marrow transplantationProcedure or surgery
conventional surgeryProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
radiation therapyRadiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2005 (estimated)
- Study startAug 2005
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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 N/A
- Primary purpose
- Treatment
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Lars M. Wagner, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00253487
- Sponsor's protocol ID
- CCHMC-04660
- Other IDs
- CDR0000446082, NCI-7036
- Status last verified
- Jan 2006
- First submitted
- 11 Nov 2005
- Last updated
- 6 Jan 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Temozolomide and O-Benzylguanine for Treatment of High-Grade Glioma, Using Autologous Peripheral Blood Stem Cells Genetically Modified for Chemoprotection
- ClinicalTrials.gov ID
- NCT00253487
- Acronym / sponsor ID
- CCHMC-04660
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult glioblastoma, adult anaplastic astrocytoma, childhood high-grade cerebral astrocytoma, adult giant cell glioblastoma, adult gliosarcoma
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2005
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 15 Nov 2005 (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.
RATIONALE: Drugs used in chemotherapy, such as temozolomide, busulfan, and O6-benzylguanine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. O6-benzylguanine may also help temozolomide work better by making tumor cells more sensitive to the drug. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy with a peripheral stem cell transplant or bone marrow transplant, using stem cells from the patient that are genetically-modified in the laboratory to protect them from the side effects of chemotherapy, may allow more chemotherapy to be given so that more tumor cells are killed. Giving combination chemotherapy and radiation therapy together with a peripheral stem cell transplant or bone marrow transplant may kill more tumor cells.
PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating younger patients who are undergoing an autologous stem cell transplant for newly diagnosed gliomas.
Detailed description
OBJECTIVES:
Primary
- Determine the safety and feasibility of a conditioning regimen comprising temozolomide, radiotherapy, and busulfan followed by an infusion of autologous stem cells genetically modified with the MGMT gene and temozolomide and O6-benzylguanine in younger patients with newly diagnosed high-grade gliomas.
Secondary
- Determine the tolerability of intrapatient dose escalation of temozolomide, in terms of transgene expression, in patients treated with this regimen.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is a pilot study.
- Surgery: Patients undergo biopsy or surgical debulking of the tumor. Two to six weeks later, patients proceed to stem cell mobilization and apheresis.
- Autologous stem cell mobilization and apheresis: Patients receive filgrastim (G-CSF) subcutaneously or IV once daily for at least 4 days before apheresis and continuing until apheresis is complete. Patients undergo apheresis for up to 4 consecutive days until a target number of 5 X 10^6 CD34-positive peripheral blood stem cells (PBSCs) are collected. Patients with insufficient numbers of PBSCs either undergo bone marrow harvest to collect a sufficient number of cells or are removed from the study. The cells are selected for CD34-positive cells which are cryopreserved for later use. Patients then proceed to chemoradiotherapy.
- Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42 and undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four to eight weeks later, patients proceed to the low-intensity, nonmyeloablative conditioning regimen.
- Autologous PBSC or bone marrow transduction: Peripheral blood or bone marrow CD34-positive stem cells are transduced with the MGMT gene on day -4.
- Low-intensity, nonmyeloablative conditioning regimen: Patients receive busulfan IV over 2 hours on days -3 and -2. Patients then proceed to autologous PBSC or bone marrow infusion.
- Autologous PBSC or bone marrow infusion: Patients undergo autologous stem cell infusion using transduced PBSCs or bone marrow on day 0. Three to six weeks later, patients proceed to chemotherapy.
- Chemotherapy: Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide once daily on days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to O6-benzylguanine may receive temozolomide alone. Patients not experiencing dose-limiting toxicity and who have at least 5% transduced neutrophils by peripheral blood analysis after course 1 receive escalating doses (intrapatient) of temozolomide during courses 2-6. Some patients undergo second-look surgery after the first course of chemotherapy.
After completion of study therapy, patients are followed monthly for 3 months, every 3 months for 3 years, every 6 months for 4 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 1-2 years.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 5 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| O6-benzylguanine | Drug | – |
| busulfan | Drug | – |
| temozolomide | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| autologous bone marrow transplantation | Procedure or surgery | – |
| conventional surgery | Procedure or surgery | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 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.
Lars M. Wagner, MD principal investigator
Children's Hospital Medical Center, Cincinnati
Questions about this trial
What is this clinical trial studying?
A study testing O6-benzylguanine, busulfan and temozolomide in people with Brain and Central Nervous System Tumors, run by Children's Hospital Medical Center, Cincinnati.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 6 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
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 6 Jan 2014.