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Myelodysplastic Syndromes (MDS)Phase 2Aza-ENCT01488565

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

A Phase 2 study testing Azacitidine and eltrombopag in people with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukaemia (AML), run by Peter MacCallum Cancer Centre, Australia at 2 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine and eltrombopag
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesAustralia
Study dates
Dec 2010to May 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

  • Peter MacCallum Cancer Centre

    East Melbourne, Victoria, 3002

  • Cabrini Hospital

    Malvern, Victoria, 3144

Other trials in Australia

About this study

Official title: A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndrome / Acute Myeloid Leukaemia, With Eltrombopag Support for Thrombocytopenia.

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.

Read more

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.

Being tested
Azacitidine and eltrombopag
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Azacitidine and eltrombopagDrug

    Also called Vidaza (azacitidine), Revolade (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.

Study groups in NCT01488565
Study groupRoleWhat they receive
Azacitidine and EltrombopagExperimentalVidaza (azacitidine) Revolade (eltrombopag)
Receives: Drug: Azacitidine and eltrombopag

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: At 6 cycles of therapy (approx 6 months)

Secondary outcomes (2)

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

    Measured: Approximately 2.5 years after the last accrued patient completes study treatment

  2. 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

    Measured: Approximately 2.5 years after last accrued patient completes study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2011 (estimated)
  2. Study startDec 2010
  3. Primary completionMay 2014
  4. Study completionMay 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01488565
Sponsor's protocol ID
10/78
Acronym
Aza-E
Status last verified
Feb 2016
First submitted
29 Nov 2011
Last updated
15 Feb 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine and eltrombopag in people with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukaemia (AML), run by Peter MacCallum Cancer Centre, Australia at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01488565.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2016.

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