Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) Overlap Syndromes Cancer
Conditions
Interventions
Patients will be randomised via a computer system, the site staff will log on to the study portal in order to randomise a patient between best supportive care and the experimental arm (ASTX727).
Pati
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. =18 years of age at the time of trial entry 2. Morphologically confirmed diagnosis of MDS/MPN (excluding JMML), in accordance with WHO 2016 diagnostic criteria, with any of the following characteristics: 2.1. CMML-2 disease stage [CMML only] 2.2. CPSS [Such et al Blood 2013] or CPSS-Mol [Elena et al Blood 2016] score of intermediate-2 or high risk [CMML only] 2.3. Other patients with one or more of the following: 2.3.1. Bone Marrow blasts >10% (including promonocytes) 2.3.2. Adverse risk cytogenetics (as defined by CPSS or MDS R-IPSS) 2.3.3. WCC =50 (or =30 with symptoms attributable to myeloproliferation) 2.3.4. RBC transfusion dependence with pre-transfusion Hb /=30ml/min/1.73m². 7. Patient willing and able to comply with scheduled visits,treatment plan and other study procedures. 8. Patient able to provide written informed consent for the trial
Exclusion criteria
Exclusion criteria: 1. Patients eligible for intensive chemotherapy and/or allogeneic haematopoietic stem cell transplantation (HSCT). 2. CMML with eosinophilia and 5q33 abnormality. 3. Previous cytotoxic chemotherapy for MDS/MPN, except hydroxycarbamide. 4. Prior hypomethylating agent exposure. 5. Transformation to AML (=20% myeloid blasts in bone marrow or peripheral blood at screening). 6. Prior organ transplantation, including allogeneic haematopoietic stem cell transplant (HSCT). 7. Known or suspected central nervous system disease involvement. 8. Known history of clinically significant or uncontrolled cardiac disease, including recent history (within 6 months) of unstable angina, acute myocardial infarction, NYHA class III or IV congestive cardiac failure, or clinically significant arrhythmia. 9. Other active malignancy, not including localized non-melanoma skin cancer, cervical carcinoma in situ, breast ductal carcinoma in situ of the breast, or localized prostate cancer controlled with hormone therapy. Patients with history of other cancers should be free of disease without ongoing anti-neoplastic therapy for at least 2 years. 10. Receipt of wide-field radiotherapy (including therapeutic radioisotopes) =28 days or limited field radiation for palliation =14 days prior to starting any study medications (or has not recovered from side effects of such therapy). 11. Active,uncontrolled infection. Patients with infection under control with active treatment are eligible. 12. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry). 13. Females of childbearing potential, and their partners, not willing to use adequate contraception during and for up to 6 months after treatment. 14. Any other concurrent serious or unstable medical, psychiatric, familial, geographic or sociological condition that in the investigator’s opinion would jeopardise the patient’s ability to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Best overall response at end of Cycle 6, defined as the patient experiencing Complete Remission (CR), Partial Remission (PR), Marrow Response (MR) or Clinical Benefit (CB) according to the IWG MDS/MPN response criteria. Any patient for whom neither response assessment (post Cycle 2; post Cycle 6) is recorded will be classed as a non-responder. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Response will be assessed according to the IWG MDS/MPN response criteria at the end of cycles 2 and 6.. Patients will be classed as responding if they achieve complete remission (CR), partial remission (PR), marrow response (MR) or clinical benefit (CB). Patients with no response assessment available will be classed as a non-responder. 2. Transformation-free survival (TFS) defined as time from entry to the trial to time of transformation to AML or death. Patients who are alive and have not transformed to AML at the time of the analysis will be censored at date last seen. TFS will be assessed as time from study entry to time of transformation to AML or death. 3. Progression-free survival (PFS) defined as time from entry to the trial to first documentation of progressive disease (PD), as defined by the 2015 IWG MDS/MPN response criteria, or death from any cause. Patients who are alive and progression free at the time of analysis will be censored at their date last seen. PFS will be assessed from time of study entry to time of progressive disease. 4. Overall Survival (OS) defined as time between trial entry and date of death from any cause. Patients who are alive at the time of analysis will be censored at date last seen. OS will be assessed as time from study entry to date of death. 5. Treatment-related toxicity defined as the number of patients who experience one or more grade 3 or greater adverse event or serious adverse event of any grade. Toxicity will be assessed from start of trial treatment to 28 days post treatment discontinuation. 6. Quality of life assessed using EQ5D-5L and the MPN-SAF tools at baseline, cycle 3, cycle 6, 1 year post randomisation and thereafter every 6 months in patients continuing on treatment. | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed