Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00351975
Status:
COMPLETED
Last Update Posted:
2014-12-23
First Post:
2006-07-13
Brief Title:
Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I Study of PXD101 in Combination With Azacitidine 5-Aza for Advanced Hematologic Malignancies
Status:
COMPLETED
Status Verified Date:
2013-10
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 phase I trial is studying the side effects and best dose of belinostat when given together with azacitidine in treating patients with advanced hematologic cancers or other diseases Belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer Drugs used in chemotherapy such as azacitidine work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Giving belinostat together with azacitidine may kill more cancer cells
Detailed Description:
PRIMARY OBJECTIVES
I Determine the maximum tolerated dose of PXD101 belinostat when given in combination with azacitidine when azacitidine is utilized at a dose range where its effects on cellular differentiation are known to be predominant in patients with advanced hematologic cancers or other diseases
SECONDARY OBJECTIVES
I Identify any additive or synergistic effects of this regimen on pharmacodynamic parameters including apoptosis and re-expression of specific target genes
II Assess any evidence of clinical activity complete remission partial remission hematologic improvement stable disease of this regimen in these patients
OUTLINE This is a dose-escalation study of belinostat followed by a randomized study
Patients receive azacitidine subcutaneously SC and belinostat intravenously IV over 30 minutes on days 1-5 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of belinostat until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity After the MTD is determined additional patients with myelodysplastic syndromes MDS or acute myeloid leukemia with trilineage dysplasia or arising from MDS are randomized to 1 of 2 treatment arms
Arm I Patients receive azacitidine SC on days 1-5
Arm II Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5
In both arms courses repeat every 28 days in the absence of disease progression or unacceptable toxicity After receiving one course patients randomized to arm I may crossover to receive treatment on arm II
For patients enrolled in the randomized portion of the study bone marrow aspirates are obtained at baseline and after course 1 for correlative studies Samples are examined by gene expression analysis of p15 and p21 DNA methylation of p15INK4B and apoptosis by RT-PCR and flow cytometry Pharmacodynamic assays are also performed
After completion of study treatment patients are followed periodically for up to 2 years
I Determine the maximum tolerated dose of PXD101 belinostat when given in combination with azacitidine when azacitidine is utilized at a dose range where its effects on cellular differentiation are known to be predominant in patients with advanced hematologic cancers or other diseases
SECONDARY OBJECTIVES
I Identify any additive or synergistic effects of this regimen on pharmacodynamic parameters including apoptosis and re-expression of specific target genes
II Assess any evidence of clinical activity complete remission partial remission hematologic improvement stable disease of this regimen in these patients
OUTLINE This is a dose-escalation study of belinostat followed by a randomized study
Patients receive azacitidine subcutaneously SC and belinostat intravenously IV over 30 minutes on days 1-5 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of belinostat until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity After the MTD is determined additional patients with myelodysplastic syndromes MDS or acute myeloid leukemia with trilineage dysplasia or arising from MDS are randomized to 1 of 2 treatment arms
Arm I Patients receive azacitidine SC on days 1-5
Arm II Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5
In both arms courses repeat every 28 days in the absence of disease progression or unacceptable toxicity After receiving one course patients randomized to arm I may crossover to receive treatment on arm II
For patients enrolled in the randomized portion of the study bone marrow aspirates are obtained at baseline and after course 1 for correlative studies Samples are examined by gene expression analysis of p15 and p21 DNA methylation of p15INK4B and apoptosis by RT-PCR and flow cytometry Pharmacodynamic assays are also performed
After completion of study treatment patients are followed periodically for up to 2 years
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 |
|---|---|---|---|
| U01CA062491 | NIH | CTEP | httpsreporternihgovquickSearchU01CA062491 |
| NCI-2009-00146 | REGISTRY | None | None |
| UCCRC-14510A | None | None | None |
| NCI-7285 | None | None | None |
| CDR0000486418 | None | None | None |
| 14510A | OTHER | None | None |
| 7285 | OTHER | None | None |
| U01CA069852 | NIH | None | None |
| U01CA132123 | NIH | None | None |
| P30CA014599 | NIH | None | None |