A Phase Ib study of eltrombopag and azacitidine in patients with high risk myelodysplastic syndromes and related disorders

Phase 1

Completed

• Conditions: Cancer; Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Miscellaneous; Myelodysplastic syndromes

• Registration Number: ISRCTN05858391
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-07-05
• Study Completion: 2020-08-31
• Last Update Posted: 5 August 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

1. Age >=16 years of age
2. Platelet count at baseline <150 x 109/l
3. Myelodysplastic Syndromes (MDS) classified as Intermediate 2 risk or high risk according to the International Prognostic Scoring System (IPSS) at registration 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 blast
4. Subjects must have platelet count and platelet transfusion data available over a period of 4 weeks prior to registration
5. A baseline bone marrow examination to evaluate blast percentage, karyotype and assessment of fibrotic change within 8 weeks of registraton
6. Alanine Aminotransferase ALT/Aspartate Aminotransferase (AST) < 3 x upper limit of normal ECOG = 2
7. Valid informed consent
Target Gender: Male & Female ; Lower Age Limit 16 years

Exclusion Criteria

1. AML with >30% blasts
2. Known HIV positive
3. Known liver cirrhosis
4. Uncontrolled infection (grade 4 CTCAE v4)
5. Previous exposure to azacitidine
6. Previous exposure to thrombomimetic agents
7. Use of prior investigational agents within 6 weeks
8. Other severe, concurrent diseases or mental disorders
9. 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
10. Bone marrow fibrosis
11. Clinical evidence of splenomegaly
12. Known hypersensitivity to study drugs or any of their excipients
13. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry)
14. Females of childbearing potential (i.e. not postmenopausal
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.
15. 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
16. 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
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of eltrombopag in combination with azacitidine; Timepoint(s): Within 5 weeks (1 cycle) of azacitidine treatment