Trial record 6 of 1375 for:    "Myelodysplastic syndromes"

Belinostat in Treating Patients With Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00357162
First received: July 26, 2006
Last updated: May 2, 2014
Last verified: December 2011
  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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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



Secondary Outcome Measures:
  • 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 2010
Primary Completion Date: December 2010 (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:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357162

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
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, NCI-2009-00143, MAYO-MC0581, NCI-7258, CDR0000489197, MC0581, 7258, P30CA015083, N01CM62205
Study First Received: July 26, 2006
Results First Received: February 13, 2013
Last Updated: May 2, 2014
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 July 24, 2014