A Multicenter Study on the Treatment of MDS/MPN Overlap Syndrome With AZA or Rux Combined With Selinexor

Prospective, Multicenter Study on the Treatment of Myelodysplastic Neoplasms (MDS)/Myeloproliferative Neoplasms (MPN) Overlap Syndrome With Azacitidine or Ruxolitinib Combined With Selinexor

This study is a prospective, multicenter, open label cohort study involving MDS/MPN patients. The enrolled patients have symptoms that require treatment, which are classified according to their clinical conditions as follows: those with MDS as the main manifestation are treated with Azacitidine combined with Selinexor; For those with MPN as the main manifestation, treatment with Selinexor combined with Ruxolitinib is used.

Study Overview

• Status: Enrolling by invitation
• Conditions: MDS
• Intervention / Treatment: Drug: Azacitidine or Ruxolitinib combined with Selinexor

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Bing Han

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Meets the diagnostic criteria of MDS/MPN (WHO 2022 edition)
2. Age ≥ 18 years old;
3. There are indications that require treatment, such as symptomatic anemia, decreased blood cells, splenomegaly, and constitutional symptoms;
4. ECOG score 0-2;
5. No stem cell transplantation plan within 6 months;
6. Liver function: Within 21 days before the start of treatment, total bilirubin<2 times the upper limit of normal (ULN), alanine aminotransferase (ALT)<2.5 times ULN;
7. Renal function: Within 21 days before the start of treatment, creatinine clearance rate ≥ 30 mL/min, calculated using Cockcroft and Gault formulas;
8. Patients receiving erythropoietin therapy or rituximab must be at a stable dosage and have stable transfusion therapy or hemoglobin levels within 8 weeks prior to entering the study.
9. Female patients with fertility must agree to the use of dual contraception methods and have a negative serum pregnancy test during screening. Male patients who have sexual intercourse with women with fertility must use effective barrier contraception methods.
10. Those who meet the requirements of the ethics committee and sign the informed consent form; Willing and able to comply with clinical visit and research related procedures.

Exclusion Criteria:

1. Those who have undergone major surgery within 4 weeks before the start of treatment,
2. those with severe liver and kidney dysfunction;
3. Patients who have undergone splenectomy in the past;
4. Patients with unstable cardiovascular function: symptomatic cardiac ischemia, uncontrolled significant conduction abnormalities, congestive heart failure (CHF) with NYHA functional class ≥ 3 or myocardial infarction within 6 months, unstable angina, unstable arrhythmia;
5. Uncontrolled active infections require systemic use of antibiotics, antiviral drugs, or antifungal drugs within one week prior to the first administration; Allow the use of prophylactic antibiotics.
6. Known active hepatitis A, B, or C infection; Or known to be positive for HCV RNA or HBsAg (HBV surface antigen); Known HIV seropositivity;
7. Patients with obvious gastrointestinal lesions or obstruction, or uncontrolled vomiting or diarrhea.
8. At baseline, peripheral neuropathy was ≥ grade 2 (within 21 days before the first day of the first cycle).
9. History of epileptic seizures, movement disorders, or cerebrovascular accidents (within 1 year before the first day of the first cycle)
10. Evidence of AML (≥ 20% of primitive cells in bone marrow or peripheral blood) according to WHO definition
11. Patients with other active malignant tumors
12. Pregnant and lactating women;
13. Fertility capable women or men who are unwilling to take effective contraceptive measures before the first dose/treatment, during the study period, and for at least 6 months after the last dose;
14. Patients without autonomous behavioral ability, such as psychiatric patients; Other situations deemed unsuitable for inclusion by researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Azacitidine or Ruxolitinib combined with Selinexor

Drug: Azacitidine or Ruxolitinib combined with Selinexor; The initial dose of Selinexor combined with Azacitidine for the treatment of MDS patients is 40mg QW, adjusted according to blood tests, with the highest dose ≤ 60mg QW.Azacitidine: The initial dose is 75 mg/m ², administered subcutaneously or intravenously, with a cycle of 1-7 days and 28 days until ineffective or intolerant.; Selinexor combined with Ruxolitinib for the treatment of patients with MPN symptoms: Selinexor dose: 40mg QW; Adjust according to the blood count, with a maximum dose of ≤ 60mg QW. Initial dose of Ruxolitinib: platelet count>100 × 109/L before enrollment, initial dose is 15 mg BID; Platelets range from 50-100 × 109/L, with an initial dose of 10 mg BID. Until ineffective or intolerant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at 6 months of treatment	ORR at 6 months of treatment	6 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 6, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: October 9, 2024
• First Submitted That Met QC Criteria: October 29, 2024
• First Posted (Actual): October 30, 2024

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Azacitidine
• Other Study ID Numbers: K6812

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes