Haematologic Neoplasms
Conditions
Interventions
Sponsors
Hibi Kazushige
Eligibility
Inclusion criteria
Inclusion criteria: - Participants with relapsed/refractory MDS or relapsed/refractory dysplastic CMML, with peripheral blasts or bone marrow blasts less than 20%, who received one or more prior lines of therapy as per standard of care. Diagnosis must be histologically confirmed as per the WHO 2016 classification of myeloid neoplasms. - Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. - Participants must have symptomatic disease that requires therapy and allows for objective efficacy assessments. - Willing to provide baseline bone marrow aspirate (or biopsy if dry-tap). - Contraceptive use by participants or participant partners should be consistent with local regulations and also comply with Clinical Study Protocol requirements. - All women of childbearing potential must have a negative serum pregnancy test result at Screening.
Exclusion criteria
Exclusion criteria: - Prior treatment with IRAK inhibitors or inhibitors of the inflammasome pathway. - Received any antineoplastic therapy (except hydroxyurea) within 15 days prior to first dose. - Received any strong or moderate Cytochrome P450 3A (CYP3A) inhibitors within 15 days prior to first dose. - Received major surgery within 28 days prior to first dose, or still recovering from surgery. - Received drugs that are known to prolong corrected QT interval (QTc) and with known risk of Torsades de Pointes, within 15 days prior to first dose. - Received immunosuppressive medications (including Graft-Versus Host Disease prophylaxis) within 28 days prior to first dose, or within 15 days in the case of systemic steroids (doses exceeding 10 mg/day of prednisone or equivalent). - Received live attenuated vaccines within 28 days prior to first dose. - Active major bleeding event. - Any evidence of systemic disease, significant clinical disorder, or laboratory finding that make undesirable the participation in the study. - Mean resting corrected QT interval using Fridericia's formula (QTcF) is greater than 450 ms obtained from triplicate Electrocardiograms (ECGs) and averaged, recorded within 5 minutes. In the presence of bundle branch block, QTcF greater than 470 ms is applicable. - History of intracranial bleeding within 6 months prior to first dose. - Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism or excretion of oral therapy. - History of a prior non-haematologic neoplasm (with some exceptions). - Unresolved Grade greater than 2 toxicities from prior anticancer therapies (with some exceptions). - Concurrent enrolment in another clinical study (with some exceptions). - Known hypersensitivity to study intervention or its excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with dose limiting toxicity (DLT) Number of participants with Adverse events (AEs) and serious AEs Duration of exposure Relative dose intensity | — |
Countries
Australia, Japan, South Korea, Spain, United Kingdom, United States
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed