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

Phase 2

• Conditions: Relapsed Acute Myeloid Leukemia; Minimal Residual Disease; Refractory Acute Myeloid Leukemia
• Interventions: Drug: Venetoclax, Decitabine, Azacytidine, Cytarabine

• Registration Number: NCT05362942
• Lead Sponsor: Beijing 302 Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-04-20
• Status Verified: 2022-05
• Study Start: 2022-05-01
• Study First Submitted QC: 2022-05-04
• Last Update Submitted: 2022-05-04
• Study First Posted: 2022-05-05
• Last Update Posted: 2022-05-05
• Primary Completion: 2023-04-30
• Study Completion: 2024-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. 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.

2. The toxic and side effects caused by the last treatment should be recovered.

3. Eastern Cooperative Oncology Group score of 0 to 3 points.

4. 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.

5. Karnofsky≥70.

6. The expected survival period is at least 12 weeks.

7. Non-pregnant, non-breastfeeding women.

Exclusion Criteria

1. Suffering from other untreated or unrelieved malignant tumors within 2 years.
2. Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication.
3. 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.
4. Patients who are unwilling or unable to comply with the protocol.
5. Currently being treated with other systemic anti-tumor or anti-tumor research drugs.
6. Women who are pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
venetoclax + Hypomethylation agent + low-dose cytarabine treatment group	Venetoclax, Decitabine, Azacytidine, Cytarabine	patients treated with venetoclax combined with decitabine/azacytidine and low-dose cytarabine

Primary Outcome Measures

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

Secondary Outcome Measures

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