Anaplastic Astrocytoma (WHO Grade III) Clinical Trial
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.
| Status | Terminated |
| Enrollment | 1 |
| Est. completion date | August 2012 |
| Est. primary completion date | December 2008 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 5 Years to 55 Years |
| Eligibility |
Inclusion Criteria: 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 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. Exclusion Criteria: 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. 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). |
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
| Country | Name | City | State |
|---|---|---|---|
| United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
| Lead Sponsor | Collaborator |
|---|---|
| Children's Hospital Medical Center, Cincinnati |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | 5 years | Yes | |
| Secondary | Assess the efficiency of gene transfer and durability of transgene expression in this clinical setting. | 5 years | Yes | |
| Secondary | 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. | 5 years | Yes |