Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy for Acute Myeloid Leukemia

Study Overview
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Brief Summary
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Although studies are ongoing to evaluate the efficiency and safety of venetoclax-based therapy, alone or in combination with hypomethylation agent or low-dose cytarabine, in relapsed/refractory acute myeloid leukemia, data are scarce and heterogenous. In this study, the investigators aimed to assess safety and response to a new venetoclax-based triple-drug combination regimen (venetoclax + hypomethylation agent + low-dose cytarabine) in acute myeloid leukemia patients who had relapsed/refractory disease or positive minimal residual disease.

Detailed Description
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Although the promising activity of venetoclax-based therapy is well demonstrated in the treatment of previously untreated elderly or unfit patients with acute myeloid leukemia, there are few data on the efficacy of venetoclax-based salvage therapy in relapsed/refractory patients, which can be difficult to treat. To date, data on venetoclax as monotherapy or in combination with hypomethylation agent or low-dose cytarabine as a salvage regimen in relapsed/refractory AML are scarce and heterogenous. In this study, the investigators aimed to assess safety and efficiency of a new triple-drug combination regimen, venetoclax + hypomethylation agent + low-dose cytarabine, in patients with relapsed/refractory acute myeloid leukemia or persistent positive minimal residual disease in the salvage setting.

Official Title
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A Study of Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy in Patients With Acute Myeloid Leukemia Who Had Relapsed/Refractory Disease or Positive Minimal Residual Disease

Conditions
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Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Minimal Residual Disease

Intervention / Treatment
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* Drug: Venetoclax, Decitabine, Azacytidine, Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 years old, voluntarily participate in clinical research and sign an informed consent form and be willing to follow and be able to complete all experimental procedures. The toxic and side effects caused by the last treatment should be recovered. Eastern Cooperative Oncology Group score of 0 to 3 points. The organ function is intact. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (Upper Limit of Normal). Creatinine≤1.5×ULN. Bilirubin≤1.5×ULN. Karnofsky≥70. The expected survival period is at least 12 weeks. Non-pregnant, non-breastfeeding women. Exclusion Criteria: Suffering from other untreated or unrelieved malignant tumors within 2 years. Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication. Suffering from any other known serious and/or uncontrolled disease (eg, uncontrolled diabetes; cardiovascular disease, including congestive heart failure New York Heart Association [NYHA] Class III or IV, 6 months patients with myocardial infarction and poorly controlled blood pressure); chronic renal failure; or active uncontrolled infection); the investigators considered unsuitable for this clinical trial. Patients who are unwilling or unable to comply with the protocol. Currently being treated with other systemic anti-tumor or anti-tumor research drugs. Women who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 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: venetoclax + Hypomethylation agent + low-dose cytarabine treatment group<br>patients treated with venetoclax combined with decitabine/azacytidine and low-dose cytarabine | Drug: Venetoclax, Decitabine, Azacytidine, Cytarabine<br>* Venetoclax was given at a dose of 400 mg/day for 28 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days (n=3) or azacytidine (n=8) was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. Cytarabine was given at a dose of 10 mg/m2 twice daily for 7 days.<br>* Other names: Cytarabine (Cytarabine hydrochloride);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate | percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi) | At the end of Cycle 2 (each cycle is 28 days) | 
| Complete minimal residual disease (MRD) Response Rate | Percentage of subjects with MRD negative or MRD < 0.01% | At the end of Cycle 2 (each cycle is 28 days) | 
| MRD Response Rate | Percentage of subjects with MRD < 0.1% detectable by multicolor flow cytometry | At the end of Cycle 2 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-Free Survival | Time interval from leukemia free state to the first recurrence or death | 24 months | 
| Overall Survival | Time interval from start of treatment until death or last follow-up | 24 months | 
| Duration of response | Time interval from morphologic/MRD response to loss of response or death | 24 months | 
| Adverse events | Number of subjects with adverse events | start of treatment to 2 weeks after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venetoclax, Hypomethylation agent, Cytarabine