A dose finding study of eltrombopag when given in combination with azacitidine for patients with high-risk Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukaemia (CMML-2) and Acute Myeloid Leukaemia (AML) with less than 30% blasts.

• Conditions: High-risk Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukaemia (CMML-2) and Acute Myeloid Leukaemia (AML) with less than 30% blasts.; MedDRA version: 18.0Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10009018Term: Chronic myelomonocytic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-000341-39-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-31
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

• Age =16 years of age
• Platelet count at baseline <150 x 109/L
• Myelodysplastic Syndromes (MDS) classified as Intermediate 2-risk or high risk according to the International Prognostic Scoring System (IPSS) at registration [2] OR
• Chronic Myelomonocytic Leukaemia (CMML) with 10-29% bone marrow blasts without proliferation (peripheral white blood cell count <13 x 109/L) OR
• Acute Myeloid Leukaemia (AML) with 20-30% bone marrow blasts
• Subjects must have a minimum of two platelet and haemoglobin counts available from a period of up to 8 weeks prior to registration, as well as a record of any platelet transfusions conducted during that period.
• A baseline bone marrow examination to evaluate blast percentage, karyotype and assessment of fibrosis within 8 weeks prior to registration
• ALT/AST < 3 x upper limit of normal
• ECOG = 2
• Valid informed consent
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

• AML with >30% blasts
• Patients who have received allogeneic bone marrow transplant
• Known HIV positive
• Known liver cirrhosis
• Uncontrolled infection (grade 4 CTCAE v4)
• Previous exposure to azacitidine
• Previous exposure to thrombomimetic agents
• Use of prior investigational agents within 4 weeks
• Other severe, concurrent diseases or mental disorders that in the opinion of the investigator make the patients unsuitable for the trial
• Concurrent active or previous malignancy within the last 3 years – except controlled, localised prostate cancer on hormone therapy or non-melanoma skin malignancy or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ
• Grade 4 bone marrow fibrosis according to the European consensus[3]
• Clinical evidence of splenomegaly
• Known hypersensitivity to study drugs or any of their excipients
• Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry)
• Females of childbearing potential (i.e. not post-menopausal or surgically sterilised) who are not willing to use adequate methods of contraception to prevent pregnancy or abstain from heterosexual activity for the duration of the trial and for at least 3 months following treatment discontinuation.
• Male patients who are not willing to use an adequate method of contraception for the duration of the trial treatment if engaged in sexual activity with a female of childbearing potential and for at least 3 months following treatment discontinuation
• Patients of east Asian ancestry*
* Patients will be excluded if either parent is East Asian (such as Chinese, Japanese, Taiwanese or Korean). In previous studies, the pharmacokinetics of eltrombopag in patients of East Asian ancestry differs significantly from the non-East Asian patients. The SPC for eltrombopag recommends patients receive 50% of the recommended dose. As this is a dose finding study, inclusion of these patients may impair an accurate finding of MTD and OBD that could be applied to the UK population.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified