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

NCT01488565 | Completed Phase 2 DMC

• 1 other identifier: 10/78
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Myelodysplastic Syndromes (MDS); Acute Myeloid Leukaemia (AML)

Outcome Measures

Primary Outcomes (1)

• Number of events of non-haematological toxicities related to the combination of eltrombopag and azacitidine

  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

  At 6 cycles of therapy (approx 6 months)

Secondary Outcomes (2)

• Number of patients with improved platelet counts and the dose at which this may be achieved.

  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

  Approximately 2.5 years after last accrued patient completes study treatment

Study Arms (1)

Azacitidine and Eltrombopag

EXPERIMENTAL

Vidaza (azacitidine) Revolade (eltrombopag)

Drug: Azacitidine and eltrombopag

Interventions

Azacitidine and eltrombopag DRUG

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.

Also known as: Vidaza (azacitidine), Revolade (eltrombopag)

Azacitidine and Eltrombopag

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• GlaxoSmithKline: collaborator
• Celgene Corporation: collaborator

Study Sites (2)

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Azacitidine; eltrombopag

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Michael Dickinson, Dr

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: December 8, 2011
• Study Start: December 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2015
• Last Updated: February 15, 2016

Record last verified: 2016-02

Locations

AU (2)