HAV Versus DAV/IAV Induction Regimen in Elderly Patients With AML

NCT06744556 | Active Not Recruiting Phase 2

• 1 other identifier: IIT2024095
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Acute myeloid leukemia (AML) is the most common leukemia in China, with a high incidence in elderly patients (≥60 years), who comprise over half of all cases (median age \~68 years). Elderly AML patients have a poor prognosis and carry multiple high-risk factors, with a 5-year overall survival (OS) of only 3-8%. Before the era of novel targeted agents, the classic "3+7" regimen was the standard intensive chemotherapy for eligible elderly patients, yielding an induction complete remission (CR) rate of 40-60%. Long-term survival remained poor, as most elderly patients are not candidates for allogeneic hematopoietic stem cell transplantation. Recent clinical studies have shown that combinations of novel targeted agents with hypomethylating agents improve outcomes in elderly or unfit patients. In a previously initiated multicenter, prospective, randomized controlled trial (NCT06066242), the investigators aimed to identify the optimal induction regimen for elderly fit patients with newly diagnosed AML. Preliminary data indicate that the DNR/IDA + Ara-C + venetoclax (DAV/IAV) regimen achieved a higher induction remission rate (77.3%) compared with DA/IA (3+7) or Ven + azacitidine (45-59%). However, this rate remains below that observed in younger adults (\>85%), highlighting the need for further optimization.

Conditions

AML

Keywords

Elderly Patients

Outcome Measures

Primary Outcomes (1)

• 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 1 years after the date of the last enrolled participants

Secondary Outcomes (7)

• Complete remission (CR) rate or complete remission with partial hematologic recovery (CRh) rate or complete remission with incomplete hematologic recovery (CRi) rate

  Up to approximately eight weeks afer induction therapy

• Undectable Minimal residual disease (MRD) by flow cytometry compelete remission rates after induction

  Up to approximately eight weeks afer induction therapy

• Undectable Minimal residual disease (MRD) by flow cytometry complete remission rates in the whole treatment

  up to 1 years after the date of the last enrolled participants

• Relapse-free Survival (RFS)

  Up to approximately 1 years after the date of the last enrolled participants

• 30-day postinduction mortality

  Up to approximately 30 days

Study Arms (2)

DAV/IAV

ACTIVE COMPARATOR

Induction therapy: Ara-C 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2 or Idarubicin 10mg/m2/d, d1-2 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If the treatment achieves CR/CRi/CRh, proceed directly to consolidation therapy. If the treatment does not achieve CR/CRi/CRh, enter the second induction phase with a different treatment regimen. Second Induction Phase: For patients with FLT3 or IDH1 mutations, targeted therapy can be chosen. If there is no FLT3 or IDH1 mutation or the patient is unwilling to use FLT3 or IDH1 inhibitors, switch to the HAV induction regimen. Consolidation therapy: 1\. intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older) Maintenance therapy: VA regimen: 6 courses Azacitidine 75 mg/m2/d on days 1-5, Venetoclax 400 mg on days 1-7.

Drug: daunorubicin; Drug: Venetoclax; Drug: cytarabine; Drug: azacitidine; Drug: Idarubicin

HAV

EXPERIMENTAL

Induction Therapy: Ara-C 100mg/m2/d, d1-5 HHT 2mg/m2/d, d1-5 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If CR/CRi/CRh is achieved, proceed directly to consolidation therapy. If the treatment does not reach CR/CRi/CRh, enter the second induction phase with a different treatment regimen. Second course: For patients with FLT3 or IDH1 mutations, the corresponding targeted therapy can be selected, as before. For patients without FLT3 or IDH1 mutations or those who do not want to use FLT3 or IDH1 inhibitors, the DAV/IAV induction regimen is changed. If the treatment does not reach CR/CRi/CRh after two courses, the patient is discharged. Consolidation therapy: 1\. intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older) Maintenance therapy: VA : 6 courses

Drug: Venetoclax; Drug: cytarabine; Drug: azacitidine; Drug: Homoharringtonine

Interventions

daunorubicin DRUG

Used in combination with cytarabine and venetoclax for induction therapy in DAV.

DAV/IAV

Venetoclax DRUG

Used in combination with cytarabine and daunorubicin for induction therapy in DAV.

DAV/IAV; HAV

cytarabine DRUG

Used in combination with venetoclax and daunorubicin for induction therapy in DAV or used by intermediate does for consolidation therapy.

DAV/IAV; HAV

azacitidine DRUG

Used in combination with venetoclax for maintenance therapy.

DAV/IAV; HAV

Homoharringtonine DRUG

Used in combination with cytarabine and venetoclax for induction therapy in HAV.

HAV

Idarubicin DRUG

Used in combination with cytarabine and venetoclax for induction therapy in IAV.

DAV/IAV

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Conforming to the diagnostic criteria of AML or MDS/AML by WHO (2022) or ICC.
• Age ≥ 60 years and ≤ 75 years, regardless of gender.
• The performance status assessment of the Eastern Cooperative Oncology Group (ECOG-PS) is 0 - 2.
• Meeting the requirements of the following laboratory examination indicators (performed within 7 days before treatment):
• \) Total bilirubin ≤ 1.5 times the upper limit of normal for the same age group; 2) AST and ALT ≤ 2.5 times the upper limit of normal for the same age group; 3) Serum creatinine \< 2 times the upper limit of normal for the same age group; 4) Cardiac enzymes \< 2 times the upper limit of normal for the same age group; 5) The cardiac ejection fraction determined by echocardiography (ECHO) \> 50%. The informed consent form must be signed before the initiation of all specific research procedures. It should be signed by the patient himself/herself or an immediate family member. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the disease, the informed consent form should be signed by the legal guardian or an immediate family member of the patient.

You may not qualify if:

• Acute promyelocytic leukemia accompanied by the PML-RARA fusion gene
• Acute myeloid leukemia accompanied by the RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
• Acute myeloid leukemia accompanied by the BCR-ABL fusion gene
• Retreated patients (referring to those who have previously undergone induction chemotherapy but can receive hydroxyurea for cytoreduction).
• Patients concurrently suffering from malignant tumors in other organs (requiring treatment).
• Active cardiac diseases, defined as one or more of the following:
• \) Uncontrolled or symptomatic angina pectoris history; 2) Myocardial infarction less than 6 months from the time of enrollment in the study; 3) History of arrhythmias requiring drug treatment or with severe clinical symptoms; 4) Uncontrolled or symptomatic congestive heart failure (\> NYHA Grade 2);
• \. Severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis).
• \. Those considered ineligible for enrollment by the researcher.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Interventions

Daunorubicin; venetoclax; Cytarabine; Azacitidine; Homoharringtonine; Idarubicin

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Ribonucleosides; Harringtonines; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: December 20, 2024
• Study Start: January 21, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)