Alternating Regimen of VA and Low-dose CHA in the Treatment of Unfit Newly Diagnosed AML

NCT ID: NCT07172204

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-16
• Study Completion Date: 2029-07-31

Brief Summary

This phase II trial tests how well VA alternating with low-dose CHA works in treating unfit patients with newly diagnosed acute myeloid leukemia (AML). This is a prospective, multi-centers, single arm phase II study aimed to overcome VEN resistance and achieve greater MRD negative rate, providing better control of treatment for unfit AML.

Detailed Description

This clinical study protocol investigates a novel treatment for newly diagnosed Acute Myeloid Leukemia (AML) patients ineligible to receive intensive chemotherapy (IC). Eligibility is defined as age ≥60 or age 18-59 with significant comorbidities. Key exclusions include specific AML subtypes including Acute promyelocytic leukemia (APL); FLT3-ITD mutations and active infections. The Intervention is a two-phase regimen. The Induction Phase consists of four alternating 28-day cycles of Venetoclax + Azacitidine (VA) and low-dose Cladribine + Homoharringtonine + Cytarabine (CHA). This is followed by a Maintenance Phase of 24 cycles of VA therapy. The Primary Endpoint is the rate of Minimal Residual Disease (MRD) negativity after two alternating cycles. Secondary Endpoints include composite complete remission rate, overall survival, and incidence of treatment-emergent adverse events. Clear Withdrawal Criteria are defined for situations involving unacceptable toxicity, lack of therapeutic benefit, or patient/investigator decision.

Conditions

Intensive Chemotherapy Unfit; Newly Diagnosed Acute Myeloid Leukemia (AML); Age ≥60

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VA alternating with low-CHA

single treatment arm

Group Type: EXPERIMENTAL

Alternately treated with VA/low CHA regimen

Intervention Type: DRUG

1. Induction Phase (4 alternating cycles):

Participants will receive 4 cycles of alternating therapy:

• VA Cycle:

• Venetoclax 400 mg PO daily on Days 1-28
• Azacitidine 75 mg/m² SC daily on Days 1-7
• Low-dose CHA Cycle:

• Cladribine 5 mg/m² IV daily on Days 1-3
• Homoharringtonine 1 mg/m² IV daily on Days 1-5
• Cytarabine 20 mg SC every 12 hours on Days 1-10 Alternating sequence: VA → CHA → VA → CHA → VA → CHA → VA → CHA

2. Maintenance Phase (24 months):

Following induction, participants will receive:

• Venetoclax 400 mg PO daily on Days 1-28
• Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for 24 cycles.

We aimed to compare this clinical intervention with standard VA which is:

• Venetoclax 400 mg PO daily on Days 1-28
• Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for at least 24 cycles.

Interventions

Alternately treated with VA/low CHA regimen

1. Induction Phase (4 alternating cycles):

Participants will receive 4 cycles of alternating therapy:

• VA Cycle:

• Venetoclax 400 mg PO daily on Days 1-28
• Azacitidine 75 mg/m² SC daily on Days 1-7
• Low-dose CHA Cycle:

• Cladribine 5 mg/m² IV daily on Days 1-3
• Homoharringtonine 1 mg/m² IV daily on Days 1-5
• Cytarabine 20 mg SC every 12 hours on Days 1-10 Alternating sequence: VA → CHA → VA → CHA → VA → CHA → VA → CHA

2. Maintenance Phase (24 months):

Following induction, participants will receive:

• Venetoclax 400 mg PO daily on Days 1-28
• Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for 24 cycles.

We aimed to compare this clinical intervention with standard VA which is:

• Venetoclax 400 mg PO daily on Days 1-28
• Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for at least 24 cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Understand the research and sign a written informed consent form;
• Be newly diagnosed with AML according to WHO 2022 criteria without prior treatment;
• or unwilling to undergo IC. Ineligibility for IC is defined as meeting any of the following criteria:
• Age ≥ 60 years
• Age 18-59 years but ineligible for intensive chemotherapy (IC) , meet ≥1 of the following:

• Eastern Cooperative Oncology Group (ECOG) performance status ≥2 at screening;
• Severe heart failure (congestive heart failure requiring treatment or myocardial infarction history with ejection fraction ≤50%);
• Severe pulmonary dysfunction (DLCO ≤65%, FEV1 ≤65%, dyspnea at rest, or oxygen dependence);
• Severe renal insufficiency requiring dialysis;
• Child-Pugh B or C cirrhosis, or hepatic impairment with total bilirubin >1.5×ULN;
• Mental illness requiring inpatient psychiatric treatment;
• Any comorbidity deemed by physician to contraindicate IC.

Exclusion Criteria

• Diagnosis of: AML arising from chronic myeloid leukemia (CML); myeloid sarcoma; acute promyelocytic leukemia (APL) or presence of FLT3-ITD mutations;
• Active malignancies (except adequately treated carcinoma in situ or basal cell carcinoma) within 2 years prior to Cycle 1 Day 1 (C1D1);
• Major surgery or systemic anticancer therapy within 28 days before C1D1;
• Known hypersensitivity to: Active pharmaceutical ingredients: cladribine, homoharringtonine, cytarabine, venetoclax, azacitidine; Any excipients in study drug formulations;
• GI conditions impairing oral drug absorption: Dysphagia; short-gut syndrome; gastroparesis or related disorders;
• Uncontrolled active infection;
• Controlled infection permitted if: Afebrile (<38°C) and hemodynamically stable (SBP >90 mmHg, HR <100 bpm) for ≥72 hours pre-C1D1; on non-interacting antimicrobial regimen; active HBV/HCV infection (Chronic carriers require PI approval with viral load monitoring); HIV-positive patients receiving HAART;
• Pregnancy/lactation or refusal of contraception: Negative serum β-hCG within 24h pre-C1D1;
• Psychiatric disorders or social circumstances compromising protocol compliance;
• Prior AML-directed therapy except: cytoreduction for hyperleukocytosis per institutional guidelines (hydroxyurea, leukapheresis); supportive growth factors;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Jie Sun

Principle Attending, Associated Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jie Dr. Sun, M.D, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Bone Marrow Transplantation Center of The First Affiliated Hospital, Zhejiang University School of Medicine

Shanshan Prof. Pei, Ph.D

Role: STUDY_DIRECTOR

Liangzhu Laboratory, Zhejiang University School of Medicine

Locations

Beijing Chao-Yang Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Shenzhen University General Hospital

Shenzhen, Guangdong, China

Site Status: RECRUITING

the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

the Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jie Sun

Role: CONTACT

jsun1492@zju.edu.cn

+8615305714109

Yuanyuan Dr. Zhu, M.D, Ph.D

Role: CONTACT

zhuyyzju@zju.edu.cn

86-13906514060

Facility Contacts

Honghu Zhu

Role: primary

zhuhhdoc@163.com

86+010-85230000

Lixin Wang

Role: primary

86+13718000488

Suning Chen

Role: primary

chensuning@suda.edu.cn

86+13656205608

Li Yu

Role: primary

zengyulii@126.com

86+0791-86120120

Jie Sun

Role: primary

jsun1492@zju.edu.cn

8615305714109

Other Identifiers

IIT20250072C

Identifier Type: -

Identifier Source: org_study_id