Combining Venetoclax, Azacitidine, and Homoharringtonine for treating high-risk Acute Myeloid Leukemia followed by stem cell transplant

Efficacy and Safety of Venetoclax and Azacitidine Combined With Low-Intensity Homoharringtonine Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate/High-Risk Newly Diagnosed Acute Myeloid Leukemia

This study is testing a new combination of treatments for people with high-risk Acute Myeloid Leukemia to see if it helps them get better before they have a stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, fludarabine
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06483906 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a combination treatment involving Venetoclax, Azacitidine, and Homoharringtonine for patients with intermediate and high-risk Acute Myeloid Leukemia (AML). Participants will receive two cycles of this chemotherapy regimen, and if they achieve minimal residual disease negativity, they will proceed to allogeneic hematopoietic stem cell transplantation. If minimal residual disease remains positive, they will receive two additional cycles of the same regimen before transplantation. The study aims to improve treatment outcomes for patients with high-risk AML.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 55 with intermediate or high-risk Acute Myeloid Leukemia who have not received prior treatment.

Not a fit: Patients with acute promyelocytic leukemia or those with a high comorbidity index may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and treatment outcomes for patients with high-risk AML.

How similar studies have performed: While this specific combination has not been widely tested, similar approaches in treating AML have shown promising results in other studies.

Eligibility criteria

Inclusion Criteria:

1. Age between 18 and 55 years, inclusive, regardless of gender.
2. Diagnosed with AML (excluding APL) according to the 2022 International Consensus Classification (ICC) for AML \[1\].
3. Evaluated as intermediate/high-risk AML based on the 2022 ELN AML guidelines (see Appendix 1).
4. No prior treatment for acute leukemia, including hypomethylating agents used for leukemia or myelodysplastic syndromes (MDS), except for hydroxyurea.
5. Patients must have a suitable hematopoietic stem cell donor.
6. Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2.
7. ECOG (Eastern Cooperative Oncology Group) performance status: 0-2.
8. Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:

   1. Serum creatinine ≤ 1.5x ULN (the upper limit of normal);
   2. Cardiac function: Ejection fraction ≥ 50%;
   3. Baseline oxygen saturation \> 92%;
   4. Total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 2.0 x ULN;
   5. Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%.

      9\) Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form.

Exclusion Criteria:

1. Acute promyelocytic leukemia.
2. Presence of extramedullary disease manifestations at diagnosis or during treatment, including central nervous system involvement.
3. History of malignancies other than myeloid neoplasms within the past 5 years prior to screening, except adequately treated cervical carcinoma in situ, basal cell carcinoma, squamous cell carcinoma of the skin, and localized prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery.

4\) ECOG \> 2. 5) HCT-CI score ≥ 3. 6) Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association \[NYHA\] class ≥ III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension.

7\) Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection.

8\) Conditions requiring treatment such as grade 2 or higher seizures, paralysis, aphasia, recent severe cerebral infarction, severe traumatic brain injury, dementia, Parkinson's disease, or schizophrenia.

9\) HIV-infected individuals. 10) Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy.

Patients at risk of HBV reactivation, are defined as those who are positive for hepatitis B surface antigen or core antibody without receiving antiviral therapy.

11\) History of autoimmune diseases. 12) Pregnant or breastfeeding women. 13)Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai General hospital,Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xianmin Song, MD — Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: Xianmin Song, MD

Conditions Acute Myeloid Leukemia; allogeneic hematopoietic stem cell transplantation; Venetoclax; Azacitidine; Homoharringtonine