Belinostat in Treating Patients With Myelodysplastic Syndromes
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
de Novo Myelodysplastic Syndromes Previously Treated Myelodysplastic Syndromes Secondary Myelodysplastic Syndromes |
Drug: belinostat |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome |
- Number of Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete Response (CR)
A CR is defined as a participant with bone marrow showing less than 5% myeloblasts with no evidence of dysplasia and with adequate peripheral blood counts for at least 2 months (hemoglobin > 11 g/dl, neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3) and with no blasts in the peripheral.
Partial Response (PR)
All the CR criteria except bone marrow blasts decreased by ≥ 50% over pretreatment, or a less advanced WHO classification than pretreatment.
Hematologic Improvement (HI)
A 2g/dl increase in hemoglobin for participants with <11g/dl hemoglobin at pretreatment, or an increase of >30,000/mm^3 platelets for participants with <100,000/mm^3 at pretreatment, or a 100% increase in neutrophil counts for participants with <1500/mm^3 at pretreatment
- Time to Progression [ Time Frame: Time from registration to the date of progression or last follow-up, assessed up to 3 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier.
- Overall Survival [ Time Frame: From date of registration to the date of last follow-up or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier.
- Duration of Response [ Time Frame: From the date of documented response until the date of progression or last follow-up, assessed up to 3 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier.
- Toxicity of Belinostat in Patients With Myelodysplastic Syndrome [ Time Frame: Prior to each course (every 21 days), and every 3 months for up to 3 years after completion of study treatment ] [ Designated as safety issue: Yes ]Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Reporting events deemed at least possibly related to study treatment.
| Enrollment: | 21 |
| Study Start Date: | May 2006 |
| Study Completion Date: | December 2009 |
| Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Drug: belinostat
Given IV
Other Name: PXD101
|
Detailed Description:
PRIMARY OBJECTIVES:
I. Number of confirmed responses (complete response, partial response, and hematologic improvement) during the first 12 weeks of treatment
SECONDARY OBJECTIVES:
I. Time to Progression II. Overall Survival III. Duration of Response IV. Time to Discontinuation of Treatment V. Toxicity
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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)
Contacts and Locations| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
| United States, Wisconsin | |
| University of Wisconsin Hospital and Clinics | |
| Madison, Wisconsin, United States, 53792 | |
| Principal Investigator: | Amanda Cashen | Mayo Clinic |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00357162 History of Changes |
| Obsolete Identifiers: | NCT01647009, NCT01664429 |
| Other Study ID Numbers: | NCI-2009-00143, MC0581, CDR0000489197, N01CM17104 |
| Study First Received: | July 26, 2006 |
| Results First Received: | February 13, 2013 |
| Last Updated: | March 22, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Myelodysplastic Syndromes Preleukemia Bone Marrow Diseases Hematologic Diseases Precancerous Conditions |
Neoplasms Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013