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Clinical Study Protocol of Venetoclax Combined With Azacitidine and Harringtonine in the Treatment of sAML

Primary Purpose

Secondary Acute Myeloid Leukemia

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Venetoclax；Azacitidine；Homoharringtonine

About this trial

This is an interventional treatment trial for Secondary Acute Myeloid Leukemia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1) Patients with acute myeloid leukemia (AML) newly diagnosed by bone marrow morphology and immunophenotyping (in line with the WHO 2016 diagnostic criteria), and meet any of the following conditions:
- Patients with treatment-related AML (tAML);
- AML patients with a previous history of MDS or CMML;
- AML patients with myelodysplasia-related cytogenetic abnormalities; 2) Age ≥ 18 years old, and age < 80 years old; 3) Eastern Cooperative Oncology Group (ECOG) performance status score ≤2; 4) Aspartate aminotransferase (ALT), alanine aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN), serum bilirubin ≤ 1.5 × ULN; serum creatinine ≤ 2.0 × ULN; Serum myocardial enzyme <2.0×ULN; 5) LVEF determined by echocardiography ≥50%; Obtain informed consent signed by the patient or legal representative.

Exclusion Criteria:

1) AML with central nervous system (CNS) infiltration; 2) Acute promyelocytic leukemia confirmed by bone marrow morphology or immunophenotyping; 3) Have received Venetoclax treatment in the past; 4) Those who are known to be allergic to any drugs or other ingredients in the program; 5) Currently suffering from active autoimmune disease or a history of autoimmune disease potentially involving the CNS; 6) Known human immunodeficiency virus (HIV) infection; 7) Known history of active hepatitis B or C (HBV, HCV) infection; 8) Pregnant women and women who are trying to conceive; 9) Suffering from severe and/or uncontrolled mental illness; 10) Any life-threatening disease, health condition, or organ system dysfunction that the investigator believes may compromise the safety of the subject, or create an undue risk to the research results; 11) Received major surgery within 4 weeks before randomization; Participate in other clinical investigators at the same time one month before enrollment

Sites / Locations

The First Affiliated Hospital with Nanjing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venetoclax combined with Azacitidine and Harringtonine

Arm Description

Venetoclax 100mg d1，200mg d2，400mg d3~d14； Azacitidine 75mg/m2/d，d1~d7； Homoharringtonine 2mg/d d1~d7

Outcomes

Primary Outcome Measures

Percentage of participants with complete remission (CR) and complete remission with incomplete marrow recovery (CRi)

CR is defined as absolute neutrophil count > 10^9/ L, platelets > 100×10^9/L, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of < 10^9/L or platelets < 100×10^9/L.

Secondary Outcome Measures

Partial Remission (PR) Rate Secondary Outcome Measures: Secondary Outcome Measures: Partial Remission (PR) Rate

PR is defined as bone marrow with 5%~25% blasts, at least 50% lower than the initial diagnosis.

Overall Response Rate (ORR)

Complete Remission/ Complete Remission with incomplete count recovery/ Partial Remission/ Morphologic Leukemia Free State

Rate of Minimal Residual Disease (MRD) negativity

Percentage of participants who converted to MRD < 10^-3 before initiation of consolidation therapy. MRD is measured by MFC and RT-qPCR.

Overall survival (OS)

It is measured from the date of randomization to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.

Disease-Free Survival (DFS）

It is defined as the time from the date of CR/CRi to the date of recurrence or death.

The proportion of allogeneic hematopoietic stem cell transplantation

Proportion of allogeneic hematopoietic stem cell transplantation after disease remission

Cumulative incidence of relapse (CIR)

It is measured from the date of CR/CRi to the date of relapse.

Full Information

NCT ID

NCT05513131

First Posted

August 21, 2022

Last Updated

August 21, 2022

Sponsor

The First Affiliated Hospital with Nanjing Medical University

1. Study Identification

Unique Protocol Identification Number

NCT05513131

Brief Title

Clinical Study Protocol of Venetoclax Combined With Azacitidine and Harringtonine in the Treatment of sAML

Official Title

Clinical Study Protocol of Venetoclax Combined With Azacitidine and Harringtonine in the Treatment of Secondary Acute Myeloid Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 30, 2021 (Actual)

Primary Completion Date

September 30, 2023 (Anticipated)

Study Completion Date

September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This research is being done to assess the therapeutic efficacy and safety of a promising regimen (Venetoclax combined with Azacitidine and Harringtonine) in patients with secondary AML This study involves the following: Venetoclax combined with Azacitidine and Harringtonine

Detailed Description

This is an open-label,single center, clinical trial to evaluate the efficacy and safety of Venetoclax in combination with Azacitidine and Harringtonine in patients with sAML The FDA has approved the combination therapy of Venetoclax and Decitabine/Azacitidine for elderly (> 60-year-old) patients with newly diagnosed AML not eligible for intensive chemotherapy. Venetoclax is an inhibitor of BCL-2 (B-cell lymphoma 2, a protein that initiates tumor growth, disease progression, and drug resistance), which can lead to cancer cell death. Homoharringtonine (HHT), a plant alkaloid with antitumor properties originally identified nearly 40 years ago, has a unique mechanism of action by preventing the initial elongation step of protein synthesis. HHT has been used widely in China for the treatment of chronic myeloid leukemia (CML), acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) Participants will receive 1-2 cycles of intensive treatment and followed with consolidated therapy with the same regimen of 4-6 cycles.If CR is not achieved by induction therapy, re-induction therapy can be continued, and those who have not achieved CR after re-induction therapy will withdraw from the study. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) if the patient meets the criteria for transplantation during treatment and a suitable donor exists After completion of study treatment, participants are followed up every 3 months for up to 2 years. It is expected that about 30 people will take part in this research study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Secondary Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Venetoclax combined with Azacitidine and Harringtonine

Arm Type

Experimental

Arm Description

Venetoclax 100mg d1，200mg d2，400mg d3~d14； Azacitidine 75mg/m2/d，d1~d7； Homoharringtonine 2mg/d d1~d7

Intervention Type

Drug

Intervention Name(s)

Venetoclax；Azacitidine；Homoharringtonine

Intervention Description

A cycle every 28 days Treatment with Venetoclax 100mg d1，200mg d2，400mg d3~d14； Azacitidine 75mg/m2/d，d1~d7 Homoharringtonine 2mg/d d1~d7

Primary Outcome Measure Information:

Title

Percentage of participants with complete remission (CR) and complete remission with incomplete marrow recovery (CRi)

Description

Time Frame

From randomization to the end of Cycle 1 (each cycle is 28 days)

Secondary Outcome Measure Information:

Title

Partial Remission (PR) Rate Secondary Outcome Measures: Secondary Outcome Measures: Partial Remission (PR) Rate

Description

PR is defined as bone marrow with 5%~25% blasts, at least 50% lower than the initial diagnosis.

Time Frame

From randomization to the end of Cycle 1 (each cycle is 28 days)

Title

Overall Response Rate (ORR)

Description

Complete Remission/ Complete Remission with incomplete count recovery/ Partial Remission/ Morphologic Leukemia Free State

Time Frame

From randomization to the end of Cycle 1 (each cycle is 28 days）

Title

Rate of Minimal Residual Disease (MRD) negativity

Description

Percentage of participants who converted to MRD < 10^-3 before initiation of consolidation therapy. MRD is measured by MFC and RT-qPCR.

Time Frame

From randomization to the end of Cycle 1 (each cycle is 28 days)

Title

Overall survival (OS)

Description

It is measured from the date of randomization to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.

Time Frame

From the time of randomization to time for up to 2 years

Title

Disease-Free Survival (DFS）

Description

It is defined as the time from the date of CR/CRi to the date of recurrence or death.

Time Frame

From the time of randomization to time for up to 2 years

Title

The proportion of allogeneic hematopoietic stem cell transplantation

Description

Proportion of allogeneic hematopoietic stem cell transplantation after disease remission

Time Frame

From the time of randomization to time for up to 2 years

Title

Cumulative incidence of relapse (CIR)

Description

It is measured from the date of CR/CRi to the date of relapse.

Time Frame

From the time of CR/CRi to time for up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 1) Patients with acute myeloid leukemia (AML) newly diagnosed by bone marrow morphology and immunophenotyping (in line with the WHO 2016 diagnostic criteria), and meet any of the following conditions: Patients with treatment-related AML (tAML); AML patients with a previous history of MDS or CMML; AML patients with myelodysplasia-related cytogenetic abnormalities; 2) Age ≥ 18 years old, and age < 80 years old; 3) Eastern Cooperative Oncology Group (ECOG) performance status score ≤2; 4) Aspartate aminotransferase (ALT), alanine aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN), serum bilirubin ≤ 1.5 × ULN; serum creatinine ≤ 2.0 × ULN; Serum myocardial enzyme <2.0×ULN; 5) LVEF determined by echocardiography ≥50%; Obtain informed consent signed by the patient or legal representative. Exclusion Criteria: 1) AML with central nervous system (CNS) infiltration; 2) Acute promyelocytic leukemia confirmed by bone marrow morphology or immunophenotyping; 3) Have received Venetoclax treatment in the past; 4) Those who are known to be allergic to any drugs or other ingredients in the program; 5) Currently suffering from active autoimmune disease or a history of autoimmune disease potentially involving the CNS; 6) Known human immunodeficiency virus (HIV) infection; 7) Known history of active hepatitis B or C (HBV, HCV) infection; 8) Pregnant women and women who are trying to conceive; 9) Suffering from severe and/or uncontrolled mental illness; 10) Any life-threatening disease, health condition, or organ system dysfunction that the investigator believes may compromise the safety of the subject, or create an undue risk to the research results; 11) Received major surgery within 4 weeks before randomization; Participate in other clinical investigators at the same time one month before enrollment

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Huang Fei, MD

Phone

+8615950523133

1533793080@qq.com

Facility Information:

Facility Name

The First Affiliated Hospital with Nanjing Medical University

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fei Huang, MD

Phone

+8615950523133

1533793080@qq.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Clinical Study Protocol of Venetoclax Combined With Azacitidine and Harringtonine in the Treatment of sAML

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