Alternating venetoclax+azacitidine and low-dose cladribine+homoharringtonine+cytarabine for unfit newly diagnosed AML

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This single-arm, multi-center phase II study enrolls adults with newly diagnosed AML who are ineligible for intensive chemotherapy, mainly age ≥60 or those with significant comorbidities. Participants receive four alternating 28-day induction cycles of venetoclax + azacitidine (VA) and low-dose cladribine + homoharringtonine + cytarabine (CHA), followed by up to 24 cycles of maintenance VA. The primary endpoint is the rate of minimal residual disease (MRD) negativity after two alternating cycles, with secondary endpoints including composite complete remission rate, overall survival, and treatment-emergent adverse events. The regimen is intended to overcome venetoclax resistance and improve depth of response in patients who cannot tolerate intensive chemotherapy.

Why it matters

Who can join: the full rules

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;

Where it's running

• 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

Study contacts

• Principal investigator: Jie Dr. Sun, M.D, Ph.D — Bone Marrow Transplantation Center of The First Affiliated Hospital, Zhejiang University School of Medicine
• Study coordinator: Jie Sun
• Email: jsun1492@zju.edu.cn
• Phone: +8615305714109

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.