Ignite Creation Date:
2024-05-05 @ 11:08 PM
Last Modification Date:
2024-10-26 @ 10:29 AM
Study NCT ID:
NCT01269424
Status:
COMPLETED
Last Update Posted:
2023-03-02
First Post:
2010-12-31
Brief Title:
BG TMZ Therapy of Glioblastoma Multiforme
Sponsor:
Stanton Gerson MD
Organization:
Case Comprehensive Cancer Center
Study Overview
Official Title:
06-benzylguanine BG and Temozolomide TMZ Therapy of Glioblastoma Multiforme GBM in Patients With MGMT Positive Tumors With Infusion of Autologous P140KMGMT Hematopoietic Progenitors to Protect Hematopoiesis
Status:
COMPLETED
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy such as temozolomide work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug Giving genetically modified peripheral blood stem cells during or after treatment may prevent side effects caused by chemotherapy
PURPOSE This clinical trial studies O6-benzylguanine and temozolomide in combination with genetically modified peripheral blood stem cells in treating patients with newly diagnosed glioblastoma multiforme
PURPOSE This clinical trial studies O6-benzylguanine and temozolomide in combination with genetically modified peripheral blood stem cells in treating patients with newly diagnosed glioblastoma multiforme
Detailed Description:
OBJECTIVES
Primary
To evaluate the feasibility of introducing and expressing P140K MGMT cDNA from a lentiviral-based provirus in autologous hematopoietic stem cells harvested from Glioblastoma multiforme GBM patients
To assess the safety associated with infusion of autologous hematopoietic stem cells transduced ex vivo with a lentiviral vector expressing P140K MGMT in patients with GBM
Secondary
To determine whether any patients who receive P140K MGMT-transduced CD34 cells tolerate O6-benzylguanine BG and dose-escalated temozolomide TMZ without myelosuppression
To evaluate the ability to detect P140K-transduced BG and TMZ-resistant hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K-transduced CD34 progenitors
To evaluate the feasibility of in vivo enrichment of P140K-expressing hematopoietic cells by repeated treatments of BG and TMZ at doses that appear therapeutic for GBM
To evaluate the efficacy of various types of chemotherapy with or without radiotherapy on conditioning the patients bone marrow to host the transduced autologous hematopoetic stem cells
To evaluate tumor response progression-free survival and overall survival
OUTLINE Patients are assigned to 1 of 3 treatment cohorts
Cohort 1 LV P140K MGMT gene transfer after concurrent chemoradiotherapy Patients receive radiotherapy 60cGy in 30 2cGy daily doses and TMZ 75mgm2 daily for 6 weeks cell infusion at week 7 T0 followed by BG 120 mgm2 intravenous infusion over 1h and TMZ 50 mgm2day x 5 days every 28 days starting on T28 for 6 cycles
Cohort 2 LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy Patients receive BG 120mgm2 intravenous infusion over 1h and TMZ 400 mgm2 one dose given on day T-2 or T-3 days prior to cell infusion followed within 72-96 hours by radiotherapy 60cGy in 30 2cGy daily doses and concurrent BG TMZ at 50 mgm2day x 5 days every 28 daysstarting on T28 for a total of 7 cycles of BG TMZ
Cohort 3 intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2 After completion of radiotherapy patients will receive BG TMZ at 50 mgm2day x 5 days Patients not experiencing any grade 3 toxicity will be increased to the next TMZ dose level of 65 mgm2day x 5 Subsequent dose escalation without grade 3 toxicity will be 80 mgm2day 100 mgm2day 120mgm2day and 140 mgm2day x 5 If at subsequent cycles a grade 3 or greater hematologic toxicity occurs the dose level for the next cycle will be reduced one level
Blood samples are collected periodically for replication-competent lentivirus detection and other laboratory biomarker studies
After completion of study therapy patients are followed up every 2 months
Primary
To evaluate the feasibility of introducing and expressing P140K MGMT cDNA from a lentiviral-based provirus in autologous hematopoietic stem cells harvested from Glioblastoma multiforme GBM patients
To assess the safety associated with infusion of autologous hematopoietic stem cells transduced ex vivo with a lentiviral vector expressing P140K MGMT in patients with GBM
Secondary
To determine whether any patients who receive P140K MGMT-transduced CD34 cells tolerate O6-benzylguanine BG and dose-escalated temozolomide TMZ without myelosuppression
To evaluate the ability to detect P140K-transduced BG and TMZ-resistant hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K-transduced CD34 progenitors
To evaluate the feasibility of in vivo enrichment of P140K-expressing hematopoietic cells by repeated treatments of BG and TMZ at doses that appear therapeutic for GBM
To evaluate the efficacy of various types of chemotherapy with or without radiotherapy on conditioning the patients bone marrow to host the transduced autologous hematopoetic stem cells
To evaluate tumor response progression-free survival and overall survival
OUTLINE Patients are assigned to 1 of 3 treatment cohorts
Cohort 1 LV P140K MGMT gene transfer after concurrent chemoradiotherapy Patients receive radiotherapy 60cGy in 30 2cGy daily doses and TMZ 75mgm2 daily for 6 weeks cell infusion at week 7 T0 followed by BG 120 mgm2 intravenous infusion over 1h and TMZ 50 mgm2day x 5 days every 28 days starting on T28 for 6 cycles
Cohort 2 LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy Patients receive BG 120mgm2 intravenous infusion over 1h and TMZ 400 mgm2 one dose given on day T-2 or T-3 days prior to cell infusion followed within 72-96 hours by radiotherapy 60cGy in 30 2cGy daily doses and concurrent BG TMZ at 50 mgm2day x 5 days every 28 daysstarting on T28 for a total of 7 cycles of BG TMZ
Cohort 3 intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2 After completion of radiotherapy patients will receive BG TMZ at 50 mgm2day x 5 days Patients not experiencing any grade 3 toxicity will be increased to the next TMZ dose level of 65 mgm2day x 5 Subsequent dose escalation without grade 3 toxicity will be 80 mgm2day 100 mgm2day 120mgm2day and 140 mgm2day x 5 If at subsequent cycles a grade 3 or greater hematologic toxicity occurs the dose level for the next cycle will be reduced one level
Blood samples are collected periodically for replication-competent lentivirus detection and other laboratory biomarker studies
After completion of study therapy patients are followed up every 2 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U01CA062502 | NIH | CTEPNCI | httpsreporternihgovquickSearchU01CA062502 |
| 8274 | OTHER | None | None |