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

• overall survival [ Time Frame: two years ] [ Designated as safety issue: No ]
• overall remission rate [ Time Frame: four weeks after one course of CHG or two courses of Decitabine ] [ Designated as safety issue: No ]
• disease free survival [ Time Frame: two years ] [ Designated as safety issue: No ]
• hematology toxicities [ Time Frame: within the first 4 weeks after CHG or Decitabine regimen ] [ Designated as safety issue: Yes ]
• non-hematologic toxicities [ Time Frame: within the first 4 weeks after CHG or Decitabine ] [ Designated as safety issue: Yes ]

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).

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.

• Drug: CHG regimen
  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.
  Other Name: Low dose chemotherapy
• Drug: 5-aza-deoxycytidine
  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.
  Other Name: Dacogen

• Experimental: CHG regimen
  one course of CHG regimen (low-dose cytarabine, homoharringtonine and G-CSF priming)
  Intervention: Drug: CHG regimen
• Active Comparator: Decitabine
  one course of Decitabine (5-aza-deoxycytidine,Dacogen)
  Intervention: Drug: 5-aza-deoxycytidine

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.