Clinical trial NCT06004765: Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS
Official title: A Prospective Single-center Study on the Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Myelodysplastic Syndromes
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-08-22
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: overall response rate (ORR)
timeFrame: 3, 6 months
measure: complete response rate
timeFrame: 3, 6 months
Secondary outcomes:
measure: relapse free survival (RFS)
timeFrame: 3, 6, 12, 24 months
measure: Overall survival (OS)
timeFrame: 3, 6, 12, 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking union medical college hospital
Study officials:
References:
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