Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome
18 Years
N/A
Both
de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes
Trial Information
Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome
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.
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)
Type of Study:
Interventional
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:
No
Principal Investigator
Amanda Cashen
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00143
NCT ID:
NCT00357162
Start Date:
May 2006
Completion Date:
December 2009
Related Keywords:
- de Novo Myelodysplastic Syndromes
- Previously Treated Myelodysplastic Syndromes
- Secondary Myelodysplastic Syndromes
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
| University of Wisconsin Hospital and Clinics | Madison, Wisconsin 53792-0001 |
