Status:

COMPLETED

Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

Lead Sponsor:

National Cancer Institute (NCI)

Conditions:

Accelerated Phase of Disease

Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

This phase I trial is studying the side effects and best dose of belinostat when given together with azacitidine in treating patients with advanced hematologic cancers or other diseases. Belinostat ma...

Detailed Description

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of PXD101 (belinostat) when given in combination with azacitidine (when azacitidine is utilized at a dose range where its effects on cellul...

Eligibility Criteria

Inclusion

  • Inclusion Criteria:
  • Histologically confirmed diagnosis of 1 of the following:
  • Relapsed or refractory acute myeloid leukemia (AML)
  • Relapsed or refractory acute promyelocytic leukemia (must have failed both tretinoin and arsenic trioxide)
  • Relapsed or refractory acute lymphoblastic leukemia
  • Secondary AML, including AML arising from antecedent hematologic diseases, such as myelodysplastic syndromes (MDS) or myeloproliferative disorders, OR therapy-related AML
  • Chronic myelogenous leukemia in accelerated or blast phase
  • Advanced phases of Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders, as defined by ≥ 1 of the following:
  • Presence of anemia (hemoglobin \< 10 g/dL and/or red blood cell transfusion dependent)
  • Presence of palpable splenomegaly
  • MDS, including chronic myelomonocytic leukemia
  • Must have intermediate or high-risk International Prognostic Scoring System (IPSS) scores (≥ 0.5)
  • Low-risk IPSS scores allowed provided ≥ 1 of the following criteria are met:
  • Hemoglobin \< 10 g/dL and/or red blood cell transfusion dependent
  • Platelet count \< 50,000/mm³
  • Absolute neutrophil count \< 1,000/mm³
  • Refractory disease OR no standard therapy exists
  • Evidence of AML associated with dysplasia on bone marrow histology for elderly patients (i.e., \> 60 years old) who are previously untreated and not candidates for or unwilling to undergoing induction therapy
  • No known active CNS involvement with disease
  • CALGB performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
  • ALT ≤ 3 times upper limit of normal (unless due to disease)
  • Creatinine ≤ 2 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 or Azacitidine
  • No history of allergic reactions to mannitol
  • No history of dose-limiting toxicity during prior treatment with Azacitidine
  • No concurrent uncontrolled illness including, but not limited to, the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude compliance with study requirements
  • No marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \> 500 msec)
  • No long QT syndrome
  • No uncontrolled cardiovascular disease, including the following:
  • Severe uncontrolled hypertension
  • Uncontrolled congestive heart failure related to primary cardiac disease
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled ischemic or severe valvular heart disease
  • Myocardial infarction within the past 6 months
  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 2 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
  • At least 2 weeks since prior radiotherapy
  • At least 4 weeks since prior investigational agents
  • At least 24 hours since prior hydroxyurea
  • At least 2 weeks since prior valproic acid
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No concurrent medication that may cause torsade de pointes
  • No other concurrent anticancer therapy, including chemotherapy, radiotherapy, or biological agents

Exclusion

    Key Trial Info

    Start Date :

    June 1 2006

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    March 1 2013

    Estimated Enrollment :

    56 Patients enrolled

    Trial Details

    Trial ID

    NCT00351975

    Start Date

    June 1 2006

    End Date

    March 1 2013

    Last Update

    December 23 2014

    Active Locations (4)

    Enter a location and click search to find clinical trials sorted by distance.

    Page 1 of 1 (4 locations)

    1

    University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, United States, 60637

    2

    University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, United States, 53792

    3

    University Health Network-Princess Margaret Hospital

    Toronto, Ontario, Canada, M5G 2M9

    4

    Princess Margaret Hospital

    Cashmere, Canterbury, New Zealand, 8022