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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years old. Patients with a definite diagnosis of MDS-RS and stratified as lower-risk according to IPSS-R. After at least 3 months of rhEPO treatment, with hemoglobin<90g/L, absolute neutrophil count≥1.0× 109 /L, and platelet≥30× 109 /L Unconditional hematopoietic stem cell transplantation 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: Proliferative (white blood cell count ≥12× 109 /L) chronic myelomonocytic leukemia. Complicated with active or uncontrolled infections. Complicated with other malignancies. Creatinine/transaminase ≥ 2 normal upper limit. Complicated with myelofibrosis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lenalidomide and sequential azacitidine<br>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<br>* 10mg/d *21 days, 28 days for 1 course<br>Drug: Azacitidine<br>* 75mg/m2/d*5 days, 28 days for 1 course<br>|
| Experimental: azacitidine<br>Azacitidine (75mg/m2/d*5 days, 28 days for 1 course) for at least 4 courses | Drug: Azacitidine<br>* 75mg/m2/d*5 days, 28 days for 1 course<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse free survival (RFS) | 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) | 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 |