Ignite Creation Date:
2024-05-05 @ 4:52 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00331513
Status:
COMPLETED
Last Update Posted:
2013-09-30
First Post:
2006-05-30
Brief Title:
Vorinostat and Idarubicin in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndromes
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1 Study of Suberoylanilide Hydroxamic Acid Vorinostat SAHA in Combination With Idarubicin in Relapsed or Refractory Leukemia
Status:
COMPLETED
Status Verified Date:
2013-09
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:
This randomized phase I trial is studying the side effects and best dose of vorinostat when given together with idarubicin in treating patients with relapsed or refractory leukemia or myelodysplastic syndromes Drugs used in chemotherapy such as vorinostat and idarubicin work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Giving vorinostat together with idarubicin may kill more cancer cells
Detailed Description:
OBJECTIVES
I Determine the maximum tolerated dose and dose-limiting toxicities of vorinostat SAHA in combination with standard-dose idarubicin in patients with relapsed or refractory acute myeloid leukemia acute lymphocytic leukemia myelodysplastic syndromes acute promyelocytic leukemia or chronic myelogenous leukemia in blastic phase
II Describe the clinical activity of this regimen in these patients III Determine the in vivo molecular effects of this regimen including the effects on DNA topoisomerase IIα mRNA expression and on the induction of γH2AX histone H3 and H4 acetylation as well as changes in the gene expression profile
IV Determine the pharmacokinetic characteristics of this regimen in these patients
OUTLINE
This is a randomized dose-escalation study of vorinostat SAHA Patients are randomized to 1 of 2 treatment arms
ARM I Patients receive oral SAHA three times daily on days 1-14 and idarubicin IV over 15 minutes once daily on days 1-3 Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity
ARM II Patients receive oral SAHA three times daily and idarubicin IV over 15 minutes once daily on days 1-3 Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity
Note Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity An additional 10 patients are treated at the MTD
Patients undergo blood collection and bone marrow biopsies periodically during the study for pharmacologic biomarker and genetic studies
After completion of study treatment patients are followed at 4 weeks and then periodically thereafter
I Determine the maximum tolerated dose and dose-limiting toxicities of vorinostat SAHA in combination with standard-dose idarubicin in patients with relapsed or refractory acute myeloid leukemia acute lymphocytic leukemia myelodysplastic syndromes acute promyelocytic leukemia or chronic myelogenous leukemia in blastic phase
II Describe the clinical activity of this regimen in these patients III Determine the in vivo molecular effects of this regimen including the effects on DNA topoisomerase IIα mRNA expression and on the induction of γH2AX histone H3 and H4 acetylation as well as changes in the gene expression profile
IV Determine the pharmacokinetic characteristics of this regimen in these patients
OUTLINE
This is a randomized dose-escalation study of vorinostat SAHA Patients are randomized to 1 of 2 treatment arms
ARM I Patients receive oral SAHA three times daily on days 1-14 and idarubicin IV over 15 minutes once daily on days 1-3 Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity
ARM II Patients receive oral SAHA three times daily and idarubicin IV over 15 minutes once daily on days 1-3 Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity
Note Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity An additional 10 patients are treated at the MTD
Patients undergo blood collection and bone marrow biopsies periodically during the study for pharmacologic biomarker and genetic studies
After completion of study treatment patients are followed at 4 weeks and then periodically thereafter
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 |
|---|---|---|---|
| U01CA062461 | NIH | CTEP | httpsreporternihgovquickSearchU01CA062461 |
| NCI-2009-00094 | REGISTRY | None | None |
| CDR0000472062 | None | None | None |
| 2005-0031 | OTHER | None | None |
| 6892 | OTHER | None | None |