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

NCT ID: NCT06004765

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-31
• Study Completion Date: 2025-08-31

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

10mg/d \*21 days, 28 days for 1 course

Azacitidine

Intervention Type: DRUG

75mg/m2/d\*5 days, 28 days for 1 course

azacitidine

Azacitidine (75mg/m2/d\*5 days, 28 days for 1 course) for at least 4 courses

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

75mg/m2/d\*5 days, 28 days for 1 course

Interventions

Lenalidomide

10mg/d \*21 days, 28 days for 1 course

Intervention Type: DRUG

Azacitidine

75mg/m2/d\*5 days, 28 days for 1 course

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bing Han

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Peking union medical college hospital

Beijing, , China

Countries

China

Central Contacts

Bing Han

Role: CONTACT

hanbing_li@sina.com.cn

13601059938

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Other Identifiers

Len+Aza-MDS-RS

Identifier Type: -

Identifier Source: org_study_id