Aza With or Without ATRA in Newly Diagnosed Unfit AML or Intermediate,High or Very High Risk MDS

Study Overview
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Brief Summary
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This is a randomized, open-label, multicenter study to compare the efficacy and safety of AZA with or without ATRA in newly diagnosed unfit AML or Intermediate,High or Very High Risk MDS

Detailed Description
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Newly diagnosed unfit AML and Intermediate,High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria are unable to tolerate the intensive chemo-therapy regimens due to their old age and poor physical condition, resulting in limited overall survival. Nowadays, AZA are recommended for unfit acute myeloid leukemia or myelodysplastic syndromes patients with remission rate of 30% 34%. AZA with or without all-trans retinoic acid (ATRA) can cooperatively inhibit leukemia cell proliferation , induce apoptosis and differentiation.

Official Title
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Azacitidine in Combination With or Without All-trans Retinoic Acid in Newly Diagnosed Unfit Acute Myeloid Leukemia or Intermediate,High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria

Conditions
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AML, MDS, Old Age; Debility, Hematologic Cancer

Intervention / Treatment
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* Drug: Azacitidine
* Drug: all trans retinoic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese guidelines for the diagnosis and treatment of acute myeloid leukemia (2017 edition)，excludes acute promyelocytic leukemia (M3、APL) and myelodysplastic syndromes(2017 edition) Be at least 18 years of age on day of signing informed consent Not suitable for newly diagnosed patients with intensive chemotherapy Not suitable for newly diagnosed patients with receiving hematopoietic stem cell transplantation The proportion of blast cells was below 50% in bone marrow Total white blood cell (WBC) count ≤10,000/µL；Must be able to swallow tablets Exclusion Criteria: Malignant neoplasms with other progression Serious mental illness uncooperative Refusal to join the study

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azacytidine Combined With ARTA<br>Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle with ATRA 20mg tid by po on days 1-21 of every cycle 28 days | Drug: Azacitidine<br>* Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle 28 days<br>* Other names: AZA;Drug: all trans retinoic acid<br>* ATRA 20mg tid by po on days 1-21 of every cycle 28 days<br>* Other names: ATRA;|
| Experimental: Azacytidine<br>Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle | Drug: Azacitidine<br>* Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle 28 days<br>* Other names: AZA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate （ORR) | Number of participants (responders) achieving ORR after the 6 cycle treatments，Overall response rate (ORR) based on the International Working Group (IWG)-2006 criteria, which include complete remission (CR), partial remission (PR), and major hematologic improvement (HI). | 6 months | 
| Overall survival (OS) | time from randomization to death from any cause, or last known date to be alive. | 24months | 
| Progression-free survival (PFS) | Progression-free survival (PFS) will be measured from time of enrolling in the clinical trial to the date on which disease progresses or the date on which the patient dies, whichever comes first. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent at Baseline | TI is when the participants who were transfusion dependent on RBC and/or Platelet at baseline achieve transfusion independence post baseline. TI is a period of at least 56 days with no transfusion after the date of the first dose of study drug to the last dose of study drug + 30 days, the initiation of post-treatment therapy, or death, whichever is earliest. | 6 months | 
| Incidence of systemic infections | Incidence of systemic infections | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute myeloid leukemia, myelodysplastic syndromes, all-trans retinoic acid, azacitidine