Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS

August 16, 2023 updated by: Bing Han, Peking Union Medical College Hospital

A Prospective Single-center Study on the Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS

At present, the main therapies for myelodysplastic syndromes with ring sideroblasts (MDS-RS) are red blood cell and platelet transfusion, erythropoietin (EPO), androgen, and iron chelation therapy. Lenalidomide is an immunomodulator with multiple mechanisms, including direct targeting of MDS clones, immunomodulation, erythropoiesis restoration, and angiogenesis inhibition. A Phase III, randomized, placebo-controlled trial of oral azacitidine (AZA) in lower-risk MDS reported higher rates of hemoglobin and platelet hematological improvement in patients with AZA monotherapy. Therefore, this study intended to investigate the efficacy and safety of lenalidomide and sequential AZA in the treatment of refractory MDS-RS versus azacitidine monotherapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Myelodysplastic neoplasms (MDS) are heterogeneous clonal disorders of stem cells that result in peripheral blood cytopenia and ineffective hematopoiesis, with the potential risk of the development of acute myeloid leukemia (AML). Most patients with myelodysplastic syndromes with ring sideroblasts (MDS-RS) are stratified into lower-risk groups by the revised International Prognostic Scoring System (IPSS). At present, the main therapies for MDS-RS are red blood cell and platelet transfusion, erythropoietin (EPO), androgen, and iron chelation therapy. Lenalidomide is an immunomodulator with multiple mechanisms, including direct targeting of MDS clones, immunomodulation, erythropoiesis restoration, and angiogenesis inhibition. Hypomethylating agents (HMA) like azacytidine (AZA) and decitabine (DEC), have been shown to improve survival or delay disease progression in high-risk MDS. A Phase III, randomized, placebo-controlled trial of oral AZA in lower-risk MDS reported higher rates of hemoglobin and platelet hematological improvement in patients with AZA monotherapy (24.3% vs 6.5%). Therefore, this study intended to investigate the efficacy and safety of lenalidomide and sequential azacitidine in the treatment of refractory MDS-RS versus azacitidine monotherapy.

Study Type

Interventional

Enrollment (Estimated)

138

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Peking Union Medical College Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age >18 years old.
  2. Patients with a definite diagnosis of MDS-RS and stratified as lower-risk according to IPSS-R.
  3. After at least 3 months of rhEPO treatment, with hemoglobin<90g/L, absolute neutrophil count≥1.0× 109 /L, and platelet≥30× 109 /L
  4. Unconditional hematopoietic stem cell transplantation
  5. Adequate hepatic functions with alanine transaminase (ALT)/aspartate. transaminase (AST) levels within 2 times of the normal upper limit and total bilirubin levels within 2 times of the normal upper limit.

5. No active infection; Not pregnant or breastfeeding 6. ECOG≦2 with an expected life span of more than 6 months 7. Documented patient consent.

Exclusion Criteria:

  1. Proliferative (white blood cell count ≥12× 109 /L) chronic myelomonocytic leukemia.
  2. Complicated with active or uncontrolled infections.
  3. Complicated with other malignancies.
  4. Creatinine/transaminase ≥ 2 normal upper limit.
  5. Complicated with myelofibrosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: lenalidomide and sequential azacitidine
Lenalidomide (10mg/d *21 days, 28 days for 1 course), at least 2 courses. If effective, continue to use lenalidomide until ineffective or intolerant. Patients receive azacitidine (75mg/m2/d*5 days, 28 days for 1 course). Until progression or intolerance. At least 2 sessions of treatment are needed.
Drug: Lenalidomide
10mg/d *21 days, 28 days for 1 course
Drug: Azacitidine
75mg/m2/d*5 days, 28 days for 1 course
Experimental: azacitidine
Azacitidine (75mg/m2/d*5 days, 28 days for 1 course) for at least 4 courses
Drug: Azacitidine
75mg/m2/d*5 days, 28 days for 1 course

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall response rate (ORR)
Time Frame: 3, 6 months
Proportion of patients achieved complete response, partial response, and hematological improvement.
3, 6 months
complete response rate
Time Frame: 3, 6 months
Proportion of patients achieved complete response.
3, 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
relapse free survival (RFS)
Time Frame: 3, 6, 12, 24 months
Relapse free survival will be calculated from the date of response to the date of first recorded relapse or death from any cause.
3, 6, 12, 24 months
Overall survival (OS)
Time Frame: 3, 6, 12, 24 months
OS is calculated for all patients from the date of initial registration to the date of death from any cause.
3, 6, 12, 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2023

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

August 1, 2025

Study Registration Dates

First Submitted

August 16, 2023

First Submitted That Met QC Criteria

August 16, 2023

First Posted (Actual)

August 22, 2023

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 16, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Len+Aza-MDS-RS

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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