Bcl-2 Inhibitors Combined With Azacytidine and Chemotherapy in Elderly Patients With Previously Untreated AML

Clinical Study of Bcl-2 Inhibitors Combined With Azacytidine and Chemotherapy in Elderly Patients With Previously Untreated Acute Myeloid Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax; Drug: Azacitidine; Drug: Cladribine; Drug: Cytarabine; Drug: Idarubicin

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Long Zhao, M.M.; Phone Number: +18919128021; Email: zhaodragon@126.com

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Recruiting
      • Long Zhao
      • Contact: Long Zhao; Phone Number: +18919128021; Email: zhaodragon@126.com
      • Contact: Qiushan Li; Phone Number: +8613893690080; Email: ldyylwh@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The elderly patients(≥ 60) with AML diagnosed according to WHO criteria;
2. Participants are ineligible for induction regimen;
3. The Eastern Cooperative Oncology Group (ECOG) performance status is 0-3;
4. The patients and their families agree and sign the informed consent form.

Exclusion Criteria:

1. Previous treatment for AML (including hypomethylating agents and other chemotherapy drugs);
2. Infiltration of the central nervous system;
3. Drugs use history affecting CYP3A within 7 days before enrollment;
4. participants considered by the investigator to be unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: ABT-199; Drug: Azacitidine; given sc.; Other Names: 5-Azacytidine; Drug: Cladribine; given ivgtt.; Other Names: 2-CdA; Drug: Cytarabine; given sc or ivgtt.; Other Names: Ara-c; Drug: Idarubicin; given ivgtt.; Other Names: Idamycin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival will be defined as the number of days from the date of first dose to the date of death.	up to 16 months.
CR/CRi	To assess the percentage of patients achieving CR/CRi according to the International Working Group criteria for AML.	up to 16 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response	To assess the percentage of patients achieving CR/CRi or partial remission (PR) according to the International Working Group criteria for AML.	up to 16 months.
Duration of response	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.	up to 16 months.
Mortality	The proportion of patients from enrollment to death was recorded.	up to 16 months.
Recurrence rate	Record the proportion of patients with recurrence in the study.	up to 16 months.
Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	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.

Collaborators and Investigators

• Sponsor: LanZhou University
• Investigators: Principal Investigator: Long Zhao, M.M., The First Hospital of Lanzhou University,Lanzhou,Gansu,China

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Anticipated): January 18, 2023
• Study Completion (Anticipated): March 18, 2023

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 24, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Chemotherapy; Azacytidine; Bcl-2 Inhibitors
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Venetoclax; Azacitidine; Cytarabine; Idarubicin; Cladribine
• Other Study ID Numbers: CSBCL2; ChiCTR2100045330 (Registry Identifier: Chinese Clinical Trial Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes