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

NCT ID: NCT06744556

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-21
• Study Completion Date: 2027-06-01

Brief Summary

Acute myeloid leukemia (AML) represents the most prevalent leukemia type in China. Elderly patients (≥60 years old) have a high incidence rate, accounting for over half of all AML patients, with a median age of onset approximately 68 years. Elderly AML patients have a poor prognosis and are often accompanied with multiple high-risk factors.The 5-year overall survival (OS) is only 3-8%.

Before the advent of new targeted drugs, for elderly patients with newly diagnosed AML who were suitable for intensive chemotherapy, the most commonly used chemotherapy regimen remained the classic "3 + 7" regimen. However, the complete remission (CR) rate after induction was approximately 40-60%. The majority of elderly patients were not eligible for allogeneic hematopoietic stem cell transplantation, resulting in a relatively poor long-term survival for elderly AML patients . With the emergence of new targeted drugs, clinical studies both domestically and internationally have demonstrated that the combination of various targeted drugs and demethylating agents has achieved favorable efficacy in elderly/unsuitable for intensive chemotherapy patients with newly diagnosed AML, prolonging their survival. Previously, we initiated a multicenter, prospective, randomized controlled clinical study (registration number: NCT06066242). The aim was to explore the optimal induction regimen for elderly fit patients with newly diagnosed AML. Preliminary data revealed that the regimen of daunorubicin (DNR) or idarubicin (IDA) combined with cytarabine (Ara - C, DA/IA) + venetoclax (Ven, DAV/IAV) had a higher induction remission rate (77.3% )than the DA/IA "3 + 7" and Ven + azacitidine (AZA) regimens (45% - 59%). However, compared to the induction remission rate of young adult patients with newly diagnosed AML (> 85%), further improvement is still required.

Previous research data show that HHT enhances the inhibitory effect of Ara-c on DNA synthesis in tumor cells by influencing cell cycle regulation. The combination of HHT and Ven can jointly affect the apoptotic pathway and enhance cell apoptosis.

Therefore, this study intends to establish a prospective, randomized controlled clinical trial to compare the induction remission rates of the HHT + Ara-c + Ven (HAV) regimen with the DAV/IAV regimen, which,based on previous data, had the highest induction remission rate .

Detailed Description

This study is a multicenter, prospective, randomized, and controlled clinical trial, which intends to enroll elderly patients diagnosed with AML in accordance with the WHO (2022) or ICC standards and are suitable for intensive chemotherapy. For patients meeting the inclusion and not meeting the exclusion criteria, they will be randomly grouped and respectively receive induction therapy with either DAV/IAV (2 + 5) or HAV regimens. Patients achieving CR/CRi/CRh after induction treatment will undergo consolidation with the intermediate-dose cytarabine regimen for two courses.After completing the induction and consolidation therapy, maintenance therapy with the VA regimen for six courses will be administered; subsequently, follow-up will be conducted. Patients in the high-risk group and those with non-negative MRD are recommended to undergo allogeneic hematopoietic stem cell transplantation.

Conditions

AML

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DAV/IAV

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.

Group Type: ACTIVE_COMPARATOR

daunorubicin

Intervention Type: DRUG

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

Venetoclax

Intervention Type: DRUG

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

cytarabine

Intervention Type: DRUG

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

azacitidine

Intervention Type: DRUG

Used in combination with venetoclax for maintenance therapy.

Idarubicin

Intervention Type: DRUG

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

HAV

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

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

cytarabine

Intervention Type: DRUG

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

azacitidine

Intervention Type: DRUG

Used in combination with venetoclax for maintenance therapy.

Homoharringtonine

Intervention Type: DRUG

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

Interventions

daunorubicin

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

Intervention Type: DRUG

Venetoclax

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

Intervention Type: DRUG

cytarabine

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

Intervention Type: DRUG

azacitidine

Used in combination with venetoclax for maintenance therapy.

Intervention Type: DRUG

Homoharringtonine

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

Intervention Type: DRUG

Idarubicin

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Conforming to the diagnostic criteria of AML or MDS/AML by WHO (2022) or ICC.

2. Age ≥ 60 years and ≤ 75 years, regardless of gender.

3. The performance status assessment of the Eastern Cooperative Oncology Group (ECOG-PS) is 0 - 2.

4. Meeting the requirements of the following laboratory examination indicators (performed within 7 days before treatment):

1) 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.

Exclusion Criteria

1. Acute promyelocytic leukemia accompanied by the PML-RARA fusion gene

2. Acute myeloid leukemia accompanied by the RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene

3. Acute myeloid leukemia accompanied by the BCR-ABL fusion gene

4. Retreated patients (referring to those who have previously undergone induction chemotherapy but can receive hydroxyurea for cytoreduction).

5. Patients concurrently suffering from malignant tumors in other organs (requiring treatment).

6. Active cardiac diseases, defined as one or more of the following:

1) 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);

7. Severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis).

8. Those considered ineligible for enrollment by the researcher.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hui Wei, MD

Role: CONTACT

weihui@ihcams.ac.cn

13132507161

Facility Contacts

Hui Wei, MD

Role: primary

weihui@ihcams.ac.cn

86-13132507161

Other Identifiers

IIT2024095

Identifier Type: -

Identifier Source: org_study_id