Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00003567
Status:
TERMINATED
Last Update Posted:
2010-06-11
First Post:
1999-11-01
Brief Title:
Gene Therapy and Chemotherapy in Treating Patients With Advanced Solid Tumors or Non-Hodgkins Lymphoma
Sponsor:
Case Comprehensive Cancer Center
Organization:
Case Comprehensive Cancer Center
Study Overview
Official Title:
Mutant MGMT Gene Transfer Into Human Hematopoietic Progenitors to Protect Hematopoiesis During O6-Benzylguanine BG NSC 637037 and Carmustine Followed by Temozolomide Therapy of Advanced Solid Tumors
Status:
TERMINATED
Status Verified Date:
2010-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
slow accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Gene therapy may improve the bodys ability to fight cancer or make the cancer more sensitive to chemotherapy Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die
PURPOSE This phase I trial is studying the side effects and best dose of gene therapy together with chemotherapy in treating patients with advanced solid tumors or non-Hodgkins lymphoma
PURPOSE This phase I trial is studying the side effects and best dose of gene therapy together with chemotherapy in treating patients with advanced solid tumors or non-Hodgkins lymphoma
Detailed Description:
OBJECTIVES
Evaluate the feasibility of introducing and expressing mutant MGMT-G156A cDNA in hematopoietic progenitors taken from patients with advanced solid tumors including gliomas or non-Hodgkins lymphoma using a safety modified retroviral vector MFG
Determine the toxicity associated with reinfusion of ex vivo-transduced hematopoietic stem cells into these patients including the detection of replication competent retrovirus
Evaluate the feasibility of identifying mutant MGMT-G156A-transduced and O6-benzylguanine BG- and temzolomide-resistant hematopoietic and stromal progenitors from the bone marrow of these patients
Evaluate the feasibility of in vivo enrichment of the transduced hematopoietic progenitors in patients treated with BG and temzolomide
Evaluate the toxicity of this regimen in these patients
Determine the antitumor effect of this regimen in these patients
OUTLINE This is a dose-escalation study of CD34 stem cells and carmustine
After a negative bone marrow sampling patients receive sargramostim GM-CSF and filgrastim G-CSF subcutaneously SC once daily on days 1-5 or G-CSF twice daily alone for 4-5 days Peripheral blood progenitor cells are collected 24 hours after the last dose of growth factor injection on day 5 and also on day 6 if necessary The CD34 positive stem cells are then infected by the retroviral mutant MGMT-G156A ex vivo
Patients receive O6-benzylguanine BG IV over 1 hour followed by carmustine IV over 1 hour every 6 weeks for 5 courses assuming recovery of peripheral blood counts Approximately 72 hours after the end of the first course of chemotherapy patients receive reinfusion of retrovirally-transduced hematopoietic stem cells over 5-10 minutes Four weeks after the completion of BG and carmustine patients receive BG IV over 1 hour followed by temozolomide IV over 1 hour every 4 weeks for up to 5 courses in the absence of hematologic toxicity Patients with responding disease may continue to receive BG and temzolomide in the absence of disease progression or unacceptable toxicity provided other phase II studies indicate the safety of more than 5 courses
Cohorts of 3-6 patients receive escalating numbers of CD34 stem cells targeted for retroviral infection and escalating doses of carmustine
Patients are followed monthly for 2 months every 4 months for 8 months and then every 6 months thereafter
PROJECTED ACCRUAL A total of 12-18 patients will be accrued for this study
Evaluate the feasibility of introducing and expressing mutant MGMT-G156A cDNA in hematopoietic progenitors taken from patients with advanced solid tumors including gliomas or non-Hodgkins lymphoma using a safety modified retroviral vector MFG
Determine the toxicity associated with reinfusion of ex vivo-transduced hematopoietic stem cells into these patients including the detection of replication competent retrovirus
Evaluate the feasibility of identifying mutant MGMT-G156A-transduced and O6-benzylguanine BG- and temzolomide-resistant hematopoietic and stromal progenitors from the bone marrow of these patients
Evaluate the feasibility of in vivo enrichment of the transduced hematopoietic progenitors in patients treated with BG and temzolomide
Evaluate the toxicity of this regimen in these patients
Determine the antitumor effect of this regimen in these patients
OUTLINE This is a dose-escalation study of CD34 stem cells and carmustine
After a negative bone marrow sampling patients receive sargramostim GM-CSF and filgrastim G-CSF subcutaneously SC once daily on days 1-5 or G-CSF twice daily alone for 4-5 days Peripheral blood progenitor cells are collected 24 hours after the last dose of growth factor injection on day 5 and also on day 6 if necessary The CD34 positive stem cells are then infected by the retroviral mutant MGMT-G156A ex vivo
Patients receive O6-benzylguanine BG IV over 1 hour followed by carmustine IV over 1 hour every 6 weeks for 5 courses assuming recovery of peripheral blood counts Approximately 72 hours after the end of the first course of chemotherapy patients receive reinfusion of retrovirally-transduced hematopoietic stem cells over 5-10 minutes Four weeks after the completion of BG and carmustine patients receive BG IV over 1 hour followed by temozolomide IV over 1 hour every 4 weeks for up to 5 courses in the absence of hematologic toxicity Patients with responding disease may continue to receive BG and temzolomide in the absence of disease progression or unacceptable toxicity provided other phase II studies indicate the safety of more than 5 courses
Cohorts of 3-6 patients receive escalating numbers of CD34 stem cells targeted for retroviral infection and escalating doses of carmustine
Patients are followed monthly for 2 months every 4 months for 8 months and then every 6 months thereafter
PROJECTED ACCRUAL A total of 12-18 patients will be accrued for this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| R21CA076192 | NIH | None | None |
| P30CA043703 | NIH | None | None |
| CASE-CWRU-2Y97 | OTHER | None | None |
| NCI-T97-0060 | None | None | None |
| CASE-2Y97 | OTHER | Case Comprehensive Cancer Center | httpsreporternihgovquickSearchP30CA043703 |