Clinical trial NCT00357162: Belinostat in Treating Patients With Myelodysplastic Syndromes
Official title: Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Secondary Myelodysplastic Syndromes
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-07-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Number of Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart
timeFrame: 12 weeks
Secondary outcomes:
measure: Time to Progression
timeFrame: Time from registration to the date of progression or last follow-up, assessed up to 3 years
measure: Overall Survival
timeFrame: From date of registration to the date of last follow-up or death due to any cause, assessed up to 3 years
measure: Duration of Response
timeFrame: From the date of documented response until the date of progression or last follow-up, assessed up to 3 years
measure: Toxicity of Belinostat in Patients With Myelodysplastic Syndrome
timeFrame: Prior to each course (every 21 days), and every 3 months for up to 3 years after completion of study treatment
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Amanda Cashen
role: PRINCIPAL_INVESTIGATOR
References: