Reduced Intensive Idarubicin and Cytarabine Plus Venetoclax as First-line Treatment for Adults With Acute Myeloid Leukaemia and Myelodysplastic Syndrome

Study Overview
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Brief Summary
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Reduced intensive 3 + 5 idarubicin and cytarabine chemotherapy plus venetoclax as first-line treatment for adults with acute myeloid leukaemia and high-risk myelodysplastic syndrome

Detailed Description
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Multiple clinical trials about chemotherapy plus venetoclax in primary diagnosed AML or relapsed/refractly AML were ongoing to attempt the facility of the combination. Zu et al demostrated that full dose of 3 + 7 daunorubicin and cytarabine chemotherapy plus 8 days escalated venetoclax acheived 91% of CR/CRi with 97% 1-year overall survival and 72% 1-year event-free survival. In this trial , we try to reduced the intensive of 3 + 5 idarubicin and cytarabine chemotherapy, but prolong venetoclax to two weeks in the induction therapy in adults AML/MDS. We expect to increase the induced remission rate by extending the dosage of targeted drug venetoclax, and minimize the side effects by reducing the dose of 3 + 7 induction chemotherapy, so as to achieve the goal of high efficiency and low toxicity.

Official Title
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A Multi-center Prospective Single Arm Clinical Study of Reduced Intensive 3 + 5 Idarubicin and Cytarabine Chemotherapy Plus Venetoclax as First-line Treatment for Adults With Acute Myeloid Leukaemia and High-risk Myelodysplastic Syndrome

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: idarubicin
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-60 years had a confirmed diagnosis of previously untreated de novo acute myeloid leukaemia or high risk myelodysplastic syndrome by bone marrow examination according to the criteria presented by WHO. Eastern Cooperative Oncology Group performance status of 0-2. adequate renal and hepatic function (appendix 2 p 45), and left ventricular ejection fraction of at least 45% by echocardiography. Exclusion Criteria: younger than 18 years old, or older than 60 years old. Diagnosed as acute promyelocytic leukaemia. Pretreated with anthracycline. CNS involvement. Positive for HIV, hepatitis B virus, or hepatitis C virus. New York Heart Association cardiovascular disability status higher than grade 2 (grade 2 is defined as cardiac disorder that is asymptomatic at rest, but ordinary physical activity might result in fatigue, palpitations, dyspnoea, or angina), chronic respiratory diseases requiring continuous supplementary oxygen, inability to take oral medication or malabsorption syndrome Uncontrollable systemic infection (viral, bacterial, or fungal), Inability to sign the informed consent form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>Reduced intensive of 3 + 5 Idarubicin and Cytarabine plus Venetoclax as induction therapy | Drug: idarubicin<br>* Idarubicin 6mg/m2 d5-7<br>* Other names: Demethoxydaunorubicin;Drug: Cytarabine<br>* Cytarabine 60mg/m2 d5-9<br>* Other names: Cytosine arabinoside;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR | assessment of the composite complete remission rate (CR=CR+CRi) | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRD | assessment of bone marrow measurable residual disease by flow cytometry | Week 6 | 
| EFS | Evaluate the event-free survival | 2 years | 
| OS | Evaluated the overall survival | 2 years | 
| adverse events | Monitor of adverse events | at any time |