Clinical Study of Azacitidine Combined With Ruxolitinib in the Treatment of Higher-risk MDS/MPN

Summary

This study observes the safety and efficacy of Azacitidine (AZA) combined with ruxolitinib to treat higher-risk Myelodysplastic Syndromes∕Myeloproliferative Neoplasms(MDS/MPN)

Eligibility

Inclusion Criteria:

• According to WHO (2016) classification, researchers made the diagnosis of CMML based on clinical and morphological characteristics. Other criteria should be met: 1) Neut ≥2x109/L, PLT ≥25x109/L, 2) belongs to the following prognostic risk group according to CPSS-MOL or MMM : CPSS-MOL: inter-2 risk (2 to 3 points); high risk (≥4 points);

MMM: inter-2 risk (2.5 to 4.5 points); high risk (≥5 points), or:

* According to the WHO (2016) classification standards (Arber 2016), researchers made the diagnosis of other types of MDS/MPN (including aCML and MDS /MPN-U) based on clinical and morphological characteristics. Other criteria should be met: 1) Neut ≥2x109/L, PLT ≥25x109/L, 2) Bone marrow blasts ≥5%;
* Patients who are not suitable for hematopoietic stem cell transplantation (HSCT) according to the local medical standards and treatment guidelines;
* Patients who are suitable for Azacitidine(AZA) treatment according to the local medical standards and treatment guidelines;
* BCR-ABL positive Chronic Myelogenous Leukemia (CML) and Ph chromosomal negative classic myeloproliferative Neoplasms, such as essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are excluded;
* Age is between 18 to 80 years old;
* ALT, AST and serum bilirubin is no more than 2 times of the upper limit of normal values (ULN), serum creatinine is no more than 150 μmol/L, and serum myocardial enzyme is less than (the same age) 2 times of normal value upper limit;
* The LVEF determined by the echocardiography is no less than 50%;
* Estimated glomerular filtration rate (EGFR) is no less than 30ml · min · 1.73m2;
* Eastern Tumor Collaboration Group (ECOG) physical states score is 0 to 2;
* Informed Consent Form is signed by patients or legal agents.

Exclusion Criteria:

* BCR-ABL positive Chronic Myelogenous Leukemia (CML) and Ph chromosomal negative classic myeloproliferative Neoplasms, such as essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) ;
* Low risk or inter-1 risk CMML patients according to CPSS-MOL or MMM scores; other types of MDS/MPN with less than 5% bone marrow blasts;
* Patients with Neut\<2x109/L, PLT\<25x109/L;
* Secondary acute leukemia, myeloid sarcoma, and blast phase of aCML;
* Patients who are allergic to any drug involved in the trial;
* Pregnancy, lactating Women, and patients who are unwilling to use contraceptives;
* Patients with abnormal Liver and kidney function which exceeded the inclusion criteria;
* Patients with organic heart disease with clinical symptoms or heart dysfunction (NYHA ≥ level 2);
* Patients with other malignancies at the same time except the following situations:

Patients had received treatment for the purpose of cure and had no active malignancies for at least 5 years prior to enrollment; 2)Patients had received sufficient treatment, non-melanoma skin cancer or malignant freckles -like moles with no signs of illness (even if random grouping is less than 3 years); 3)Received sufficient treatment, in situ cancer without signs of illness (even if the random group is less than 3 years);

* Patients with AIDS, syphilis, active hepatitis B (HBV-DNA can be measured) and hepatitis C;
* Patients with cardiovascular diseases with clinical significance, such as arrhythmia that have not been controlled or have symptoms, congestive heart failure or myocardial infarction within 6 months, or level 3 (moderate) or level 4 (Severe) heart disease (NYHA according to the New York Heart Society's functional grading method);
* Patients with any situations that might interfere with research procedures or results, or have the medical status or disease that will bring a certain risk to participating in this study judged by researchers (such as activity systemic infection);
* Patients who can't understand or follow the research plan;
* Patients who are under 18 or over 80 years old;
* Patients who underwent a major surgery within 4 weeks before the random grouping;
* Patients who are participating in other clinical trials one month before joining the group;
* Patients who rely on illegal drugs;
* Patients with psychological disorders or cognitive disorders

Conditions2

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