Trials / Completed

CompletedNCT00351975

Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

A Phase I Study of PXD101 in Combination With Azacitidine (5-Aza) for Advanced Hematologic Malignancies

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 56 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Conditions

Interventions

Type	Name	Description
DRUG	Belinostat	Given IV
DRUG	Azacitidine	Given SC
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

Start date: 2006-06-01
Primary completion: 2013-03-01
Completion: 2013-03-01
First posted: 2006-07-14
Last updated: 2014-12-23

Locations

4 sites across 3 countries: United States, Canada, New Zealand

Source: ClinicalTrials.gov record NCT00351975. Inclusion in this directory is not an endorsement.