PXD101 in Treating Patients With Acute Myeloid Leukemia

Brief Title

PXD101 in Treating Patients With Acute Myeloid Leukemia

Official Title

A Phase 2 Study of PXD101 in Patients With Relapsed or Refractory Acute Myelogenous Leukemia or Patients Over 60 With Newly-Diagnosed Acute Myelogenous Leukemia

Brief Summary

      This phase II trial is studying how well PXD101 works in treating patients with relapsed or
      refractory acute myeloid leukemia or older patients with newly diagnosed acute myeloid
      leukemia. PXD101 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

      PRIMARY OBJECTIVES:

      I. Evaluate the response rate (complete response and partial response) in patients with acute
      myeloid leukemia treated with PXD101.

      SECONDARY OBJECTIVES:

      I. Evaluate the overall survival of these patients. II. Evaluate the duration of response in
      these patients. III. Evaluate the toxicity of this drug in these patients.

      TERTIARY OBJECTIVES:

      I. Evaluate molecular response to PXD101.

      OUTLINE:

      Patients receive PXD101 IV over 30 minutes on days 1-5. Treatment repeats every 21 days for
      6-12 months in the absence of disease progression or unacceptable toxicity.

      Blood and bone marrow samples are obtained before and after study treatment for laboratory
      studies.

      After completion of study treatment, patients are followed periodically for 1 year.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Complete Response Rate

Secondary Outcome

 Overall Survival

Condition

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Intervention

belinostat

Study Arms / Comparison Groups

 Treatment (belinostat)

Description:  Patients receive PXD101 IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 6-12 months in the absence of disease progression or unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

12

Start Date

May 2006

Completion Date

July 2010

Primary Completion Date

July 2009

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed acute myelogenous
             leukemia

          -  The diagnosis must be made by bone marrow aspirate and biopsy; patients must have
             routine cytochemical evaluation along with immunophenotyping done by flow cytometry;
             cytogenetic analysis must also be performed

          -  For patients age 18-59 years, at least one prior regimen of induction chemotherapy is
             required; patients who have been treated with bone marrow or stem cell transplantation
             are eligible; there is no prior therapy requirement for patients age > 60

               -  Patients for whom potentially curative treatment is available must be offered
                  this treatment and decline

          -  Life expectancy of greater than 3 months

          -  ECOG performance status =< 2 (Karnofsky >= 60%)

          -  Serum total bilirubin =< 2.0 mg/dl

          -  AST and ALT =< 2.5 times upper limit of normal (ULN)

          -  Creatinine clearance >= 60 mL/min OR creatinine < 1.5 times ULN

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity or pharmacokinetics of PXD101 will be
             determined following review of their case by the principal investigator

               -  Efforts should be made to switch patients with gliomas or brain metastases who
                  are taking enzyme inducing anticonvulsant agents to other medications

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Patients taking hydroxyurea for the purpose of cytoreduction should discontinue this
             medication at least 24 hours prior to the initiation of therapy with PXD101

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients with known central nervous system (CNS) disease should be excluded from this
             clinical trial because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to PXD101

          -  Patients may not have had prior treatment with another HDAC inhibitor within 1 week of
             initiation of therapy with PXD101; patients receiving valproic acid should stop this
             medication at least 1 week prior to therapy with PXD101

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness that could compromise compliance with study
             requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with PXD101

          -  HIV-positive patients are ineligible

          -  Patients with a marked baseline prolongation of QT/QTc interval (e.g. repeated
             demonstration of a QTc interval 500 msec), Long QT Syndrome, or the required use of
             concomitant medication on PXD101 infusion days that may cause Torsade de Pointes
             (including disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol,
             bepridil, amiodarone, arsenic trioxide, cisapride, lidoflazine, clarithromycin,
             erythromycin, halofantrine, pentamidine, sparfloxacin, domperidone, droperidol,
             chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, and methadone)

          -  Significant cardiovascular disease including unstable angina pectoris, uncontrolled
             hypertension, congestive heart failure related to primary cardiac disease, a condition
             requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a
             myocardial infarction within 6 months prior to trial entry
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Kenneth Foon, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00357032

Organization ID

NCI-2012-02838

Secondary IDs

PHII-68

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Kenneth Foon, Principal Investigator, City of Hope Medical Center

Verification Date

March 2018