Optimizing Induction Chemotherapy Regimens for ND Elderly AML Patients Who Are Eligible for Intense Chemotherapy

Optimizing Induction Chemotherapy Regimens for Newly Diagnosed Elderly Acute Myeloid Leukemia Patients Who Are Eligible for Intense Chemotherapy: A Multicenter, Randomized, Controlled Phase II Clinical Trial

The optimal induction chemotherapy regimen for newly diagnosed elderly AML patients who are eligible for intense chemotherapy is currently not well defined. Thus, we intend to conduct a multicenter, randomized, controlled clinical trial to screen the safety and efficacy of two induction regimens (Ven+AZA and DA/IA 2+5+VEN) in order to select one as the experimental arm in the sebsequent 3 phase RCT study. A total of 90 patients will be enrolled in this study and segregated into three groups with 30 in each group. Patients who achieve CR/CRi/CRh after using different induction regimens will receive the same consolidation and maintenance therapy. Allogeneic hematopoietic stem cell transplantation is recommended for patients in the high-risk group or those with persist MRD positivity. After completion of the treatment phase, patients entered the follow-up period.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Other: Different induction chemotherapy regimens

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand the study and voluntarily sign informed consent.
2. Age: 60~75 years old, gender unlimited.
3. Patients diagnosed with acute myeloid leukemia according to "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia" who haven't been treated.
4. Eastern Cooperative Oncology Group (ECOG) physical state score: 0-2.
5. Fit for intensive chemotherapy.
6. The function of main organs should meet the following standards before treatment: Kidney: serum creatinine ≤ 2× upper limit of normal range (ULN); Liver: total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5× ULN; Heart: myocardial enzymes ≤ 2× ULN and normal ejection fraction by cardiac color doppler ultrasound

Exclusion Criteria:

1. Patients with acute promyelocytic leukemia
2. Patients with RUNX1::RUNX1T1 or CBFB::MYH11 fusion gene
3. Patients with BCR::ABL fusion gene
4. Patients who have received a prior treatment for AML with chemotherapy, hypomethylating agents or venetoclax before.
5. Patients with concurrent malignant tumors requiring treatment
6. Patients with active heart disease defined as one or more of the following: (1) Uncontrolled or symptomatic angina pectoris;(2) A myocardial infarction 6 months before enrolled; (3)Arrhythmia needed medication or with severe clinical symptoms;(4)Uncontrolled or symptomatic congestive heart failure (NYHA> grade 2);(5)Left ventricular ejection fraction below the lower limit of the normal range.
7. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DA/IA 2+5+VEN; Daunorubicin or Idarubicin ×2 days, cytarabine × 5 days combined with venetoclax as induction regimen	Other: Different induction chemotherapy regimens; azacitidine combined with venetoclax or chemotherapy with or without venetoclax
Experimental: AZA+VEN; Azacitidine combined with venetoclax as induction regimen	Other: Different induction chemotherapy regimens; azacitidine combined with venetoclax or chemotherapy with or without venetoclax
Active Comparator: DA/IA 3+7; Daunorubicin or Idarubicin ×3 days combined with cytarabine × 7 days as induction regimen	Other: Different induction chemotherapy regimens; azacitidine combined with venetoclax or chemotherapy with or without venetoclax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	It is defined as the time from the start of randomization to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first).	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR) rate or complete remission with partial hematologic recovery (CRh) rate or complete remission with incomplete hematologic recovery (CRi) rate	Proportion of patients with CR, CRh or CRi	Up to approximately eight weeks
Minimal residual disease (MRD)-negative remission rates after induction	Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative	Up to approximately eight weeks
Cumulative incidence of minimal residual disease (MRD)-negative remission rates	The proportion of patients with negative MRD results at any time during treatment	Up to approximately 1 years
Relapse-free Survival (RFS)	It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up.	Up to approximately 2 years
Overall survival (OS)	It is defined as the time from the start of randomization to the death from any cause.	Up to approximately 2 years
30-day postinduction mortality	It is defined as death from any cause within 30 days after the start of induction.	Up to approximately 30 days
60-day postinduction mortality	It is defined as death from any cause within 60 days after the start of induction.	Up to approximately 60 days

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Hui Wei, MD, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): May 10, 2028

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: elderly; newly diagnosed; fit; induction regimen
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute
• Other Study ID Numbers: IIT2023059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No