Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dasatinib and Vorinostat in Treating Patients With Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00816283
Recruitment Status : Completed
First Posted : January 1, 2009
Last Update Posted : July 17, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE December 31, 2008
First Posted Date  ICMJE January 1, 2009
Last Update Posted Date July 17, 2012
Study Start Date  ICMJE September 2008
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2010)
  • Maximum tolerated dose [ Time Frame: 21 days after the beginning of treatment ]
  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 21 days from the beginning of the last course of treatment ]
  • Response rate [ Time Frame: One year after treatment completion ]
  • Objective tumor response [ Time Frame: One year after treatment completion ]
  • Survival [ Time Frame: One year after treatment completion ]
  • Time to treatment failure [ Time Frame: One year after treatment completion ]
  • Duration of response [ Time Frame: One year after treatment completion ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 31, 2008)
  • Maximum tolerated dose
  • Toxicity as assessed by NCI CTCAE v3.0
  • Response rate
  • Objective tumor response
  • Survival
  • Time to treatment failure
  • Duration of response
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dasatinib and Vorinostat in Treating Patients With Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia
Official Title  ICMJE BMS CA180157: A Phase I Combination Study of Dasatinib Plus Vorinostat in Accelerated Phase, Chronic Phase Refractory to Second Line Therapy or Blast Crisis Chronic Myelogenous Leukemia (CML), and in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)
Brief Summary

RATIONALE: Dasatinib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving dasatinib together with vorinostat may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib when given together with vorinostat in treating patients with accelerated phase or blastic phase chronic myelogenous leukemia or acute lymphoblastic leukemia.

Detailed Description

OBJECTIVES:

  • To define the maximum tolerated dose of dasatinib and vorinostat in patients with accelerated phase or blastic phase chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.
  • To assess the toxicity of this regimen in these patients.
  • To assess, preliminarily, the efficacy of this regimen in these patients.

Secondary

  • To perform correlative studies relevant to this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral dasatinib twice daily on days 1-21 and oral vorinostat twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspiration and blood sample collection periodically for correlative laboratory studies. Samples are assessed by RT-PCR for DNA damage response and proapoptotic elements (GADD45, FANC, and FOXO3A); cytogenetic analysis; flow cytometry; mutation analysis of bcr-abl; and gene expression array analysis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Drug: dasatinib
    50 mg orally 2 times per day or 140 mg orally one time per day
  • Drug: vorinostat
    100 mg orally 2 times per day
  • Genetic: cytogenetic analysis
    Performed at the end of cycle two of treatment and every six cycles for patients with accelerated CML and every 3 cycles for patients with blast crisis or Ph+ ALL
  • Genetic: gene expression analysis
    Bone marrow aspirate obtained pre-treatment, at first scheduled bone marrow assay and at relapse. Peripheral blood drawn pre-therapy, day +14 of first treatment cycle and at relapse.
  • Genetic: mutation analysis
    Performed at baseline and at every bone marrow analysis on peripheral blood
  • Genetic: reverse transcriptase-polymerase chain reaction
    Peripheral blood drawn prior to starting Vorinostat on Day 1 and on Day 14 of treatment
  • Other: flow cytometry
    Performed at the end of cycle two of treatment and every six cycles for patients with accelerated CML and every 3 cycles for patients with blast crisis or Ph+ ALL
  • Other: laboratory biomarker analysis
    Performed pre-treatment and day +14 of treatment
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 16, 2012)
5
Original Estimated Enrollment  ICMJE
 (submitted: December 31, 2008)
24
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:

    • Chronic myelogenous leukemia meeting 1 of the following criteria:

      • In accelerated phase, defined by the presence of ≥ 1 of the following:

        • At least 15% but < 30% blasts in peripheral blood and/or bone marrow
        • At least 30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that < 30% blasts are present in bone marrow)
        • At least 20% basophils in peripheral blood
        • Platelet count < 100,000/mm³ (unrelated to therapy) OR platelet count > 100,000/mm³ and unresponsive to therapy
        • Cytogenetic evidence of clonal evolution
        • Increasing spleen size and increasing WBC count and unresponsive to therapy
      • In blastic phase (blast crisis), defined by the presence of ≥ 1 of the following:

        • At least 30% blasts in peripheral blood and/or bone marrow
        • Extramedullary infiltrates of leukemic cells (other than liver or spleen involvement)
    • Philadelphia chromosome-positive acute lymphoblastic leukemia meeting any of the following criteria:

      • Newly diagnosed or relapsed disease
      • Previously treated with chemotherapy, stem cell transplantation, or tyrosine kinase inhibitors (TKIs)
  • No active CNS involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Total bilirubin < 2.0 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Serum sodium, potassium, magnesium, phosphate, and calcium ≥ lower limit of normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 4 weeks after discontinuation of study drug
  • Able to take oral medication
  • No active post-transplantation-related infections (e.g., fungal or viral infection)
  • No active acute graft-versus-host disease (GVHD) of any grade
  • No chronic GVHD (other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression)
  • No other malignancy that required radiotherapy or systemic treatment within the past 5 years
  • No concurrent medical condition that may increase the risk of toxicity, including pleural or pericardial effusion of any grade
  • No cardiac conditions, including any of the following:

    • Uncontrolled angina, congestive heart failure, or myocardial infarction within the past 6 months
    • Diagnosed congenital long QT syndrome
    • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
    • Prolonged QTc interval (i.e., QTc > 450 msec) on baseline EKG
  • No hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration
  • No history of significant bleeding disorder unrelated to cancer, including any of the following:

    • Diagnosed congenital bleeding disorder (e.g., von Willebrand's disease)
    • Acquired bleeding disorder diagnosed within the past year (e.g., acquired anti-factor VIII antibodies)
    • Ongoing or recent (i.e., within the past 3 months) significant gastrointestinal bleeding
  • No prisoners or individuals who are compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • No prior HDAC inhibitors or compounds with HDAC inhibitor-like activity (e.g., valproic acid) as anti-tumor therapy

    • Prior valproic acid for the treatment of seizures allowed provided it was not given within the past 30 days
  • Prior allogeneic stem cell transplantation allowed
  • More than 4 weeks since prior chemotherapy other than TKI (6 weeks for nitrosoureas and mitomycin)
  • More than 2 weeks since prior radiotherapy
  • At least 7 days since prior and no concurrent Category I drugs that are generally accepted to have a risk of causing Torsades de pointes, including any of the following:

    • Quinidine, procainamide, or disopyramide
    • Amiodarone, sotalol, ibutilide, or dofetilide
    • Erythromycin or clarithromycin
    • Chlorpromazine, haloperidol, mesoridazine, thioridazine, or pimozide
    • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine
  • At least 7 days since prior and no concurrent medications that directly and durably inhibit platelet function, including any of the following:

    • Aspirin or aspirin-containing combinations, clopidogrel, or dipyridamole
    • Tirofiban, epoprostenol, eptifibatide, cilostazol, abciximab, ticlopidine, or cilostazol
  • At least 5 days since prior and no concurrent St. John's wort
  • No IV bisphosphonates during the first 8 weeks of dasatinib therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00816283
Other Study ID Numbers  ICMJE 08047
P30CA033572 ( U.S. NIH Grant/Contract )
CHNMC-08047
CDR0000631569 ( Registry Identifier: NCI PDQ )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: David Snyder, MD City of Hope Comprehensive Cancer Center
PRS Account City of Hope Medical Center
Verification Date July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP