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

NCT05817955 | Recruiting Phase 2

• 1 other identifier: 2022-SR-757
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

MDS/MPN

Outcome Measures

Primary Outcomes (3)

• complete response rate

  Complete remission was achieved according to the remission criteria of MDS/MPN

  From randomization to the end of Cycle 6 (each cycle is 28 days)

• overall survival

  It is measured from the date of randomization to the date of death from any cause; patients not known to have died at least follow-up are censored on the date they were last known to be alive.

  From the time of randomization to time for up to 2 years

• overall response rate

  overall response includes all the response according to the remission criteria of MDS/MPN

  From randomization to the end of Cycle 6 (each cycle is 28 days)

Secondary Outcomes (2)

• progression-free survival

  From the time of randomization to time for up to 2 years

• Early mortality

  up to 3 months

Study Arms (1)

Azacitidine (AZA) with Ruxolitinib

EXPERIMENTAL

The treatment phase of each course of treatment is based on Azacitidine (AZA)+Ruxolitinib. Specific scheme: (1) Azacitidine+Ruxolitinib scheme: Azacitidine (AZA) 75mg · m-2 · D-1, D1 to D7, subcutaneous injection; Ruxolitinib, D1 to D28, orally, select Ruxolitinib initial dose according to platelet level: ① PLT\> 100X10\*9/L: 20mg BID orally; ② PLT (50-100) X10\*9/L: 15mg BID orally; ③ PLT \<50X10\*9/L: 10mg Bid orally. The above schemes are all 28 days of treatment. If the patient has serious adverse reactions (such as infection and bone marrow suppression), appropriately delay the next course of treatment or adjust the amount of RUXOLITINIB. Termination of the scheme treatment.

Drug: Azacitidine (AZA) with Ruxolitinib

Interventions

Azacitidine (AZA) with Ruxolitinib DRUG

1. Antibiotics: Antibiotic treatment is positively given when symptoms related to infection, and other support treatment is strengthened. 2. Blood products: Infuse the blood products according to the patient's blood routine test. Drugs that need to be used by other diseases must be recorded in detail in the case report form, including the general name of the drug, the dosage of the medication, and the frequency of administration. Drugs are not allowed to be combined: Avoiding the use of granulocyte colony-stimulating factor (G-CSF), there may be risk of spleen rupture.

Azacitidine (AZA) with Ruxolitinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Jiangbin Hospital Affiliated to Jiangsu University: collaborator
• Nanjing Second Hospital: collaborator
• Jiangning Hospital Affiliated to Nanjing Medical University: collaborator

Study Sites (1)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Interventions

Azacitidine

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Zhongxun Shi, MD

  The First Affiliated Hospital with Nanjing Medical University

  STUDY DIRECTOR

Central Study Contacts

Zhongxun Shi, MD

CONTACT

+86 13502187429; shizhongxun1@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: April 18, 2023
• Study Start: November 1, 2022
• Primary Completion: January 1, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)