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Trial record 3 of 22 for:    eltrombopag mds

A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndromes (MDS) / Acute Myeloid Leukaemia (AML), With Eltrombopag Support for Thrombocytopenia (Aza-E)

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ClinicalTrials.gov Identifier: NCT01488565
Recruitment Status : Completed
First Posted : December 8, 2011
Last Update Posted : February 15, 2016
Sponsor:
Collaborators:
GlaxoSmithKline
Celgene Corporation
Information provided by (Responsible Party):
Peter MacCallum Cancer Centre, Australia

Tracking Information
First Submitted Date  ICMJE November 29, 2011
First Posted Date  ICMJE December 8, 2011
Last Update Posted Date February 15, 2016
Study Start Date  ICMJE December 2010
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2011)
Number of events of non-haematological toxicities related to the combination of eltrombopag and azacitidine [ Time Frame: At 6 cycles of therapy (approx 6 months) ]
The number of events of Grade III/IV non-haematological toxicities will be measured based on the possibly, probably or definitely relatedness to the combination of eltrombopag and azacitidine
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2011)
  • Number of patients with improved platelet counts and the dose at which this may be achieved. [ Time Frame: Approximately 2.5 years after the last accrued patient completes study treatment ]
  • Correlation of the laboratory findings with the response of the combination of 5-azacitidine and eltrombopag in patients with MDS and low marrow blast count AML [ Time Frame: Approximately 2.5 years after last accrued patient completes study treatment ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndromes (MDS) / Acute Myeloid Leukaemia (AML), With Eltrombopag Support for Thrombocytopenia
Official Title  ICMJE A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndrome / Acute Myeloid Leukaemia, With Eltrombopag Support for Thrombocytopenia.
Brief Summary

Myelodysplastic Syndrome (MDS) is a disease of the bone marrow characterized by anemia,neutropenia, and thrombocytopenia (low red blood cell, white blood cell, and platelet counts). MDS patients with thrombocytopenia who fail standard therapies require regular platelet transfusions which are expensive and inconvenient, and are a risk for further serious bleeding complications. The new treatment of MDS using azacitidine has shown to increase the survival rate of MDS patients including to improve platelet production over time. However,in the early cycles of treatment with azacitidine,the low platelet counts tend to exacerbate before they provide any clinical benefit.

Eltrombopag is a drug designed to activate the thrombopoietin receptor. Eltrombopag has been able to increase platelet counts in healthy Thrombocytopenia Purpura (ITP), a disease where patients destroy their own platelets very rapidly and thus develop thrombocytopenia.

Eltrombopag is administered orally and is Therapeutic Goods Administration (TGA) approved for the treatment of thrombocytopenia in patients with chronic ITP who failed to respond to standard treatment.

This study is a single arm pilot study to evaluate the safety and tolerability of Eltrombopag in the treatment of low platelet counts in adult subjects with MDS treated using azacitidine This study also incorporates a correlative laboratory component designed to determined the mechanism of action of 5-azacitidine +/- Eltrombopag and to determine a baseline profile which may predict those most responsive. These studies will incorporate gene methylation and expression, and immunoprofiling.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodysplastic Syndromes (MDS)
  • Acute Myeloid Leukaemia (AML)
Intervention  ICMJE Drug: Azacitidine and eltrombopag
Standard: azacitidine D1-5, 8&9, until loss of clinical benefit. Experimental: eltrombopag at a dose ranging from 50-300mg for 6 months, continuing only in those deriving clinical benefit.
Other Names:
  • Vidaza (azacitidine)
  • Revolade (eltrombopag)
Study Arms  ICMJE Experimental: Azacitidine and Eltrombopag
Vidaza (azacitidine) Revolade (eltrombopag)
Intervention: Drug: Azacitidine and eltrombopag
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: December 6, 2011)
25
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with low platelet count (<=150 x109/L)and in addition disease diagnosis of either MDS, or nonproliferative CMML or low marrow blast count AML not suitable for induction chemotherapy
  • Age >18 years
  • ECOG score 0-2 at screening
  • Life expectancy ≥12 weeks
  • Ability to comply with the adequate contraception in patients of childbearing potential.

Exclusion Criteria:

  • Subjects with the diagnosis acute promyelocytic leukaemia
  • Prior treatment with azacitidine or any other methyl-transferase inhibitor (e.g. decitabine)
  • Prior treatment with eltrombopag, romiplostim, or other TPO-receptor agonist
  • AML or MDS requiring cytoreductive therapy (eg hydroxyurea, ara-c, thioguanine etc) in the month prior to study entry
  • Known uncontrolled medical conditions which may compromise participation in this study including but not limited to:

    • Poorly controlled congestive heart failure: ejection fraction <30% measured in past 6 months) or NYHA class IV
    • Arrhythmia known to increase the risk of thromboembolic events.
    • Unstable angina or an ischaemic cardiac event requiring hospital admission in the previous 12 months.
    • Unresolved GI disease that may significantly alter the absorption of eltrombopag
  • Known pro-thrombotic condition as defined by a history ≥1 unprovoked deep venous thrombosis or pulmonary embolism, or any DVT/PE with a procoagulant condition screen suggesting the presence of a procoagulant condition (prothrombin gene mutation homozygosity, factor V leiden homozygosity, antithrombin deficiency, lupus anticoagulant syndrome).
  • History of Ischaemic neurological event (TIA or stroke) within the preceding 2 years.
  • Inadequate renal function (eGFR <30 ml/min by Cockcroft-Gault (C-G) formula, or as measured by 24 hour urinary creatinine clearance)
  • Inadequate hepatic function:

    • bilirubin ≥1.5xULN - ≤80µmol/L acceptable if attributed to haemolysis, ineffective erythropoiesis or iron overload). This applies also for patients with Gilbert's Syndrome.
    • AST or ALT ≥2xULN (≤3xULN acceptable if attributed to transfusion-associated iron overload)
    • Patients with known liver cirrhosis.
  • Other concurrent severe and/or uncontrolled medical conditions including a history of malignancy other than MDS/AML in the preceding 2 years requiring chemotherapy and/or radiotherapy. Non melanotic skin cancers requiring low dose local radiotherapy or topical agents are allowed on study if considered clinically stable or healed.
  • Women who are pregnant or breast-feeding.
  • Treatment with growth factors such as erythropoietin, GCSF or stem cell factor in the 21 days prior to commencement of study therapy.
  • Active or uncontrolled infections.
  • Subjects with known HIV infection.
  • Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study
  • Bone marrow fibrosis that leads to an inability to aspirate marrow for quality cytological assessment, termed a "dry tap".
  • Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
  • Splenomegaly >14cm on the screening ultrasound examination.
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 Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01488565
Other Study ID Numbers  ICMJE 10/78
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Peter MacCallum Cancer Centre, Australia
Study Sponsor  ICMJE Peter MacCallum Cancer Centre, Australia
Collaborators  ICMJE
  • GlaxoSmithKline
  • Celgene Corporation
Investigators  ICMJE
Principal Investigator: Michael Dickinson, Dr Peter MacCallum Cancer Centre, Australia
PRS Account Peter MacCallum Cancer Centre, Australia
Verification Date February 2016

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