A comparison of response to treatment in patients with Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) Overlap Syndromes taking ASTX727 versus best supportive care

Phase 2

• Conditions: Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) Overlap Syndromes; Cancer

• Registration Number: ISRCTN30808508
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-13
• Last Update Posted: 8 July 2024
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 77

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 <90 g/L
2.3.5. Symptomatic anaemia (with Hb =100 g/L)
2.3.6. Thrombocytopenia (Plt =50 x 10^9/L)
2.3.7. Symptomatic splenomegaly
2.3.8. Systemic symptoms with no alternative explanation (including weight loss =10% of baseline over previous 6 months)
2.3.9. Symptomatic extramedullary involvement (e.g. skin infiltration, serous effusions)
3. Treatment-naïve for prior hypomethylating agent, intensive chemotherapy or other disease-modifying anti-neoplastic therapy (e.g. lenalidomide); patients may have received prior hydroxycarbamide,recombinant erythropoietin, danazol, interferon or anagrelide.
4. ECOG performance status of 0,1 or 2 at trial entry (Appendix 3).
5. Life expectancy of =3 months at trial entry,as assessed by the treating physician.
6. Must have adequate hepatic, renal and endocrine function during screening as demonstrated by the following:
6.1. ALT and/or AST =3x upper limit of normal (ULN);
6.2. Total bilirubin =1.5x ULN or =2x ULN if upon judgement of the treating investigator the hyperbilirubinaemia is due to extramedullary haematopoiesis related to the underlying MDS/MPN or to Gilbert’s disease;
6.3. Serum creatinine =1.5x ULN or estimated creatinine clearance >/=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

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.