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

NCT07172204 | Recruiting Phase 2

• 1 other identifier: IIT20250072C
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Keywords

Acute Myeloid Leukemia; Venetoclax; alternating; Homoharringtonine; Cladribine; age 60 and older; intensive chemotherapy unfit; newly diagnosed

Outcome Measures

Primary Outcomes (1)

• Negative rate of minimal residual lesions (MRD)

  Proportion of patients achieving MRD-negative status (≤0.1% leukemic blasts by flow cytometry) after two cycles of alternating VA/CHA therapy

  At day28 of the second alternating (one alternating is VA plus low-CHA)

Secondary Outcomes (7)

• composite complete remission, CRc

  At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)

• Overall response rate, ORR

  At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)

• Overall Survival, OS

  Time from enrollment to death from any cause, whichever came first, assessed up to 24 months

• disease-free survival, DFS

  From the date of first response until the date of relapse or death from any cause, whichever came first, assessed up to 24 months

• MRD negative DFS, DFS-MRD

  From the date of first MRD-negative status until the date of MRD-positive, relapse or death due to relapse, whichever came first, assessed up to 24months.

Study Arms (1)

VA alternating with low-CHA

EXPERIMENTAL

single treatment arm

Drug: Alternately treated with VA/low CHA regimen

Interventions

Alternately treated with VA/low CHA regimen 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.

VA alternating with low-CHA

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• AbbVie: collaborator

Study Sites (5)

Beijing Chao-Yang Hospital, Capital Medical University

Beijing, Beijing Municipality, China

RECRUITING

Shenzhen University General Hospital

Shenzhen, Guangdong, China

RECRUITING

the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

RECRUITING

the Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

RECRUITING

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

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jie Dr. Sun, M.D, Ph.D

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

  PRINCIPAL INVESTIGATOR

• Shanshan Prof. Pei, Ph.D

  Liangzhu Laboratory, Zhejiang University School of Medicine

  STUDY DIRECTOR

Central Study Contacts

Jie Sun

CONTACT

+8615305714109; jsun1492@zju.edu.cn

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

CONTACT

86-13906514060; zhuyyzju@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Attending, Associated Professor

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: September 15, 2025
• Study Start: September 16, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2029
• Last Updated: February 4, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared from the date of publication to 6 months after.
• Access Criteria: Contact the team by e-mail or other specified contact information described on publication

Locations

CN (5)