Belinostat in Treating Patients With Myelodysplastic Syndromes

NCT ID: NCT00357162

Last Updated: 2014-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2010-12-31

Brief Summary

This phase II trial is studying how well belinostat works in treating patients with myelodysplastic syndromes. 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.

Detailed Description

OBJECTIVES:

I. Establish the efficacy and safety of PXD101 (belinostat) in patients with myelodysplastic syndromes that progressed after or is ineligible for azacitidine treatment.

II. Assess the biological activity of PXD101 in these patients via assays of histone acetylation, gene expression profiling, and DNA methylation.

OUTLINE: This is a multicenter study.

Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response, partial response, or hematologic improvement after 4 courses receive 4 additional courses of therapy. After completion of study treatment, patients are followed every 3-6 months for up to 3 years.

Conditions

de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (enzyme inhibitor therapy)

Patients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

belinostat

Intervention Type: DRUG

Given IV

Interventions

belinostat

Given IV

Intervention Type: DRUG

Other Intervention Names

PXD101

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed myelodysplastic syndromes (MDS)

• De novo or secondary MDS
• Patients with < 5 % bone marrow blasts must meet ≥ 1 of the following criteria:

• Symptomatic anemia with either hemoglobin < 10.0 g/dL or required RBC transfusions within the past 3 months
• Thrombocytopenia with ≥ 2 platelet counts < 50,000/mm³ or significant hemorrhage requiring platelet transfusions
• Neutropenia with ≥ 2 absolute neutrophil counts < 1,000/mm³
• No acute myeloid leukemia (≥ 20% bone marrow blasts)
• ECOG performance status 0-2
• Life expectancy > 12 weeks
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 2 times ULN
• Creatinine ≤ 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101
• No HIV positivity
• QTc interval ≤ 500 msec
• No long QT syndrome
• No significant cardiovascular disease, including any of the following:

• Unstable angina pectoris
• Uncontrolled hypertension
• Congestive heart failure related to primary cardiac disease
• Condition requiring anti-arrhythmic therapy
• Ischemic or severe valvular heart disease
• Myocardial infarction within the past 6 months
• No other uncontrolled serious medical condition (e.g., cardiac arrhythmias or diabetes)
• Recovered from prior therapy
• No more than 2 prior therapies for MDS

• Prior hematopoietic growth factors, androgens, and other supportive care agents allowed and are not considered in the prior therapy total
• No prior allogeneic stem cell transplantation
• More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• No prior histone deacetylase (HDAC) inhibitors for treatment of MDS
• More than 2 weeks since prior valproic acid or other HDAC inhibitors
• No other concurrent investigational agents
• No concurrent medication that may cause torsades depointes, including any of the following:

• Disopyramide
• Dofetilide
• Ibutilide
• Procainamide
• Quinidine
• Sotalol
• Bepridil
• Methadone
• Amiodarone hydrochloride
• Arsenic trioxide
• Cisapride
• Calcium-channel blockers (e.g., lidoflazine)
• Anti-infective agents (i.e., clarithromycin, erythromycin, halofantrine, pentamidine, or sparfloxacin)
• Domperidone or droperidol
• Antipsychotic agents (i.e., chlorpromazine, haloperidol, mesoridazine, thioridazine, or pimozide)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amanda Cashen

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

NCI-2009-00143

Identifier Type: REGISTRY

Identifier Source: secondary_id

MAYO-MC0581

Identifier Type: -

Identifier Source: secondary_id

NCI-7258

Identifier Type: -

Identifier Source: secondary_id

CDR0000489197

Identifier Type: -

Identifier Source: secondary_id

MC0581

Identifier Type: OTHER

Identifier Source: secondary_id

7258

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62205

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00143

Identifier Type: -

Identifier Source: org_study_id

NCT01647009

Identifier Type: -

Identifier Source: nct_alias

NCT01664429

Identifier Type: -

Identifier Source: nct_alias