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Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome

Phase 2
18 Years
Not Enrolling
de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes

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Trial Information

Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome


I. Number of confirmed responses (complete response, partial response, and hematologic
improvement) during the first 12 weeks of treatment


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.

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

- 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

- 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)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart

Outcome Description:

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

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Amanda Cashen

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

May 2006

Completion Date:

December 2009

Related Keywords:

  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Secondary Myelodysplastic Syndromes
  • Myelodysplastic Syndromes
  • Preleukemia



Mayo Clinic Rochester, Minnesota  55905
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001