- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05513131
Clinical Study Protocol of Venetoclax Combined With Azacitidine and Harringtonine in the Treatment of sAML
Clinical Study Protocol of Venetoclax Combined With Azacitidine and Harringtonine in the Treatment of Secondary Acute Myeloid Leukemia
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Huang Fei, MD
- Phone Number: +8615950523133
- Email: 1533793080@qq.com
Study Locations
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Jiangsu
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Nanjing, Jiangsu, China, 210000
- Recruiting
- The First Affiliated Hospital with Nanjing Medical University
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Contact:
- Fei Huang, MD
- Phone Number: +8615950523133
- Email: 1533793080@qq.com
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Venetoclax combined with Azacitidine and Harringtonine
Venetoclax 100mg d1,200mg d2,400mg d3~d14; Azacitidine 75mg/m2/d,d1~d7; Homoharringtonine 2mg/d d1~d7
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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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of participants with complete remission (CR) and complete remission with incomplete marrow recovery (CRi)
Time Frame: From randomization to the end of Cycle 1 (each cycle is 28 days)
|
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.
|
From randomization to the end of Cycle 1 (each cycle is 28 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Partial Remission (PR) Rate Secondary Outcome Measures: Secondary Outcome Measures: Partial Remission (PR) Rate
Time Frame: From randomization to the end of Cycle 1 (each cycle is 28 days)
|
PR is defined as bone marrow with 5%~25% blasts, at least 50% lower than the initial diagnosis.
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From randomization to the end of Cycle 1 (each cycle is 28 days)
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Overall Response Rate (ORR)
Time Frame: From randomization to the end of Cycle 1 (each cycle is 28 days)
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Complete Remission/ Complete Remission with incomplete count recovery/ Partial Remission/ Morphologic Leukemia Free State
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From randomization to the end of Cycle 1 (each cycle is 28 days)
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Rate of Minimal Residual Disease (MRD) negativity
Time Frame: From randomization to the end of Cycle 1 (each cycle is 28 days)
|
Percentage of participants who converted to MRD < 10^-3 before initiation of consolidation therapy.
MRD is measured by MFC and RT-qPCR.
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From randomization to the end of Cycle 1 (each cycle is 28 days)
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Overall survival (OS)
Time Frame: From the time of randomization to time for up to 2 years
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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.
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From the time of randomization to time for up to 2 years
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Disease-Free Survival (DFS)
Time Frame: From the time of randomization to time for up to 2 years
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It is defined as the time from the date of CR/CRi to the date of recurrence or death.
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From the time of randomization to time for up to 2 years
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The proportion of allogeneic hematopoietic stem cell transplantation
Time Frame: From the time of randomization to time for up to 2 years
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Proportion of allogeneic hematopoietic stem cell transplantation after disease remission
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From the time of randomization to time for up to 2 years
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Cumulative incidence of relapse (CIR)
Time Frame: From the time of CR/CRi to time for up to 2 years
|
It is measured from the date of CR/CRi to the date of relapse.
|
From the time of CR/CRi to time for up to 2 years
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplastic Processes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Neoplasm Metastasis
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Protein Synthesis Inhibitors
- Venetoclax
- Azacitidine
- Homoharringtonine
Other Study ID Numbers
- 2022-SR-376
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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