Bcl-2 Inhibitors Combined With Azacytidine and Chemotherapy in Elderly Patients With Previously Untreated AML
Study Details
Study Description
Brief Summary
In this prospective study, 30 newly untreated elderly patients with acute myeloid leukemia(AML) who were not suitable for standard chemotherapy were enrolled to observe the efficacy and side effects of venetoclax (VEN) combined with azacytidine (AZA) and chemotherapy in newly treated elderly patients with AML. Overall survival (OS), complete remission rate/complete remission with incomplete recovery of blood cell count (CR/ CRi) were used as the primary endpoints, and time to response (TTR), duration of response (DOR), mortality, and recurrence rate were used as secondary endpoints,and the incidence of adverse events were evaluated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
Detailed Description
Induction therapy: venetoclax d1 100mg, d2 200mg, d3-28 400mg, po; azacytidine 75mg/m2, d1-7, sc. Consolidation therapy: Regimen A or B was chosen according to the wishes of the patients. In addition, venetoclax was used for 14 days for positive minimal residual disease(MRD) and 7 days for MRD negative.
regimen A: the first two cycles: venetoclax 400mg, d1-7/14, po; cladribine 5mg/m2, d1-3, ivgtt; cytarabine 10mg/m2, q12h, d1-10, sc; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; regimen B: the first two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 100mg/m2, d1-5/7, ivgtt; idarubicin 8mg/m2, d1-2/3, ivgtt; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; If the patient's ECOG performance status ≥2, the reduction of regimen IA(cytarabine+idarubicin)was 5+2. Maintenance therapy: azacytidine 75mg/m2, d1-7, sc.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Venetoclax group Induction therapy: venetoclax d1 100mg, d2 200mg, d3-28 400mg, po; azacytidine 75mg/m2, d1-7, sc. Consolidation therapy: Regimen A or B was chosen according to the wishes of the patients. In addition, venetoclax was used for 14 days for positive minimal residual disease(MRD) and 7 days for MRD negative. regimen A: the first two cycles: venetoclax 400mg, d1-7/14, po; cladribine 5mg/m2, d1-3, ivgtt; cytarabine 10mg/m2, q12h, d1-10, sc; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; regimen B: the first two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 100mg/m2, d1-5/7, ivgtt; idarubicin 8mg/m2, d1-2/3, ivgtt; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; If the patient's ECOG performance status ≥2,the reduction of regimen IA(cytarabine+idarubicin)was 5+2. Maintenance therapy: azacytidine 75mg/m2, d1-7, sc. |
Drug: Venetoclax
given po.
Other Names:
Drug: Azacitidine
given sc.
Other Names:
Drug: Cladribine
given ivgtt.
Other Names:
Drug: Cytarabine
given sc or ivgtt.
Other Names:
Drug: Idarubicin
given ivgtt.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall survival (OS) [up to 16 months.]
Overall survival will be defined as the number of days from the date of first dose to the date of death.
- CR/CRi [up to 16 months.]
To assess the percentage of patients achieving CR/CRi according to the International Working Group criteria for AML.
Secondary Outcome Measures
- Time to response [up to 16 months.]
To assess the percentage of patients achieving CR/CRi or partial remission (PR) according to the International Working Group criteria for AML.
- Duration of response [up to 16 months.]
Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease.
- Mortality [up to 16 months.]
The proportion of patients from enrollment to death was recorded.
- Recurrence rate [up to 16 months.]
Record the proportion of patients with recurrence in the study.
- Adverse events [Adverse events were assessed weekly during the first and second cycles, and every two cycles thereafter (each cycle is 28 days), up to 16 months.]
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
The elderly patients(≥ 60) with AML diagnosed according to WHO criteria;
-
Participants are ineligible for induction regimen;
-
The Eastern Cooperative Oncology Group (ECOG) performance status is 0-3;
-
The patients and their families agree and sign the informed consent form.
Exclusion Criteria:
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Previous treatment for AML (including hypomethylating agents and other chemotherapy drugs);
-
Infiltration of the central nervous system;
-
Drugs use history affecting CYP3A within 7 days before enrollment;
-
participants considered by the investigator to be unsuitable for inclusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Long Zhao | Lanzhou | Gansu | China | 730000 |
Sponsors and Collaborators
- LanZhou University
Investigators
- Principal Investigator: Long Zhao, M.M., The First Hospital of Lanzhou University,Lanzhou,Gansu,China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CSBCL2
- ChiCTR2100045330