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

Phase 4

Not yet recruiting

• Conditions: Myelodysplastic Syndromes
• Interventions: Drug: Lenalidomide; Drug: Azacitidine

• Registration Number: NCT06004765
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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 Timeline

• Status Verified: 2023-08
• Study Start: 2023-08
• Study First Submitted: 2023-08-16
• Study First Submitted QC: 2023-08-16
• Last Update Submitted: 2023-08-16
• Study First Posted: 2023-08-22
• Last Update Posted: 2023-08-22
• Primary Completion: 2024-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 138

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.

6. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
lenalidomide and sequential azacitidine	Lenalidomide	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.
lenalidomide and sequential azacitidine	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.
azacitidine	Azacitidine	Azacitidine (75mg/m2/d\*5 days, 28 days for 1 course) for at least 4 courses

Primary Outcome Measures

Name	Time	Method
complete response rate	3, 6 months	Proportion of patients achieved complete response.
overall response rate (ORR)	3, 6 months	Proportion of patients achieved complete response, partial response, and hematological improvement.

Secondary Outcome Measures

Name	Time	Method
relapse free survival (RFS)	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.
Overall survival (OS)	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.

Trial Locations

Locations (1)

Peking union medical college hospital; 🇨🇳 Beijing, China