Efficacy Study of CHG Regimen vs Decitabine to Treat Higher-risk MDS

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of CHG regimen (low-dose cytarabine, homoharringtonine with G-CSF priming) to decitabine in the treatment of higher-risk myelodysplastic syndromes(MDS).

Detailed Description
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Patients with higher-risk myelodysplastic syndrome (MDS) have a survival rate of 0.4 to 1.2 years as well as a high risk of their disease progressing to acute myeloid leukemia (AML). The only treatment with a curative potential is allogeneic stem cell transplantation. However, in the majority of patients, this treatment is not applicable, mainly due to the age of the recipients and comorbid conditions. Low-dose chemotherapy CHG regimen (low-dose cytarabine, homoharringtonine with G-CSF priming)has been used to treat higher-risk MDS in China and achieve high response rate. Hypomethylating agents 5-aza-2'-deoxycytidine (decitabine) is nucleoside analogs that covalently bind to the DNA methyltransferases, irreversibly inhibiting their function, leading to the progressive loss of methylation and reversal of gene silencing. The purpose of this study is to compare the efficacy and safety of CHG regimen to Decitabine in higher-risk MDS.

Official Title
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Phase 2/3 Study of Efficacy Study of CHG Regimen vs Decitabine to Treat Higher-risk MDS

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: CHG regimen
* Drug: 5-aza-deoxycytidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age rang from 16 to 80 years; diagnosis of higher-risk MDS (with≥ 5% blast in bone marrow); a performance status of 0-3 according to the Eastern Cooperative Oncology Group (ECOG); no evidence of severe concurrent cardiac, pulmonary, neurologic, or metabolic diseases; adequate hepatic (serum bilirubin level <2×upper normal limit) and renal (serum creatinine <2×upper normal limit) function tests. Exclusion Criteria: Female with pregnancy; a performance of 4-5 according to ECOG score; HIV positive; uncontrolled severe fungal infection or tuberculosis; with other progressive malignant diseases.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHG regimen<br>one course of CHG regimen (low-dose cytarabine, homoharringtonine and G-CSF priming) | Drug: CHG regimen<br>* cytarabine (25mg/d, days1-14) and homoharringtonine (1mg/d, days1-14) by intravenous continuous infusion, G-CSF (300 μg/d) by subcutaneous injection from day 0 until neutrophil count recovery to 2.0× 109/L.<br>* Other names: Low dose chemotherapy;|
| Active Comparator: Decitabine<br>one course of Decitabine (5-aza-deoxycytidine,Dacogen) | Drug: 5-aza-deoxycytidine<br>* Decitabine (5-aza-deoxycytidine)for injection, 20mg/m2/day, IV (in the vein) on days 1-5 of each 28 day cycle, Number of Cycles: 2.<br>* Other names: Dacogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate |  | four weeks after one course of CHG or two courses of Decitabine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | two years | 
| overall remission rate |  | four weeks after one course of CHG or two courses of Decitabine | 
| disease free survival |  | two years | 
| hematology toxicities |  | within the first 4 weeks after CHG or Decitabine regimen | 
| non-hematologic toxicities |  | within the first 4 weeks after CHG or Decitabine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myelodysplastic syndromes, Decitabine, homoharringtonine, cytarabine, G-CSF