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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Not yet enrolling; Phase 4

Conditions: Myelodysplastic Syndromes

Treatments: Drug: Lenalidomide; Drug: Azacitidine

Study type: Interventional

Funder types: Other

Identifiers

NCT06004765

Len+Aza-MDS-RS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 138 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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138 participants in 2 patient groups

lenalidomide and sequential azacitidine

Experimental group

Description:

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.

Treatment:

Drug: Azacitidine

Drug: Lenalidomide

azacitidine

Experimental group

Description:

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

Treatment:

Drug: Azacitidine