Clinical trial NCT06483906: Venetoclax and Azacitidine Combined With Homoharringtonine, Followed by Allo-HSCT for Intermediate and High-risk AML.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
allogeneic hematopoietic stem cell transplantation
Venetoclax
Azacitidine
Homoharringtonine
Lead sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2024-07-03
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single-center, single-arm, prospective phase II clinical trial evaluating the efficacy and safety of the VAH (Venetoclax and Azacitidine combined with Homoharringtonine) regimen, followed by allo-HSCT for intermediate and high-risk AML. Eligible patients receive two cycles of the VAH chemotherapy regimen. If minimal residual disease (MRD) is negative after these two cycles, patients proceed to the transplantation process. If MRD remains positive, patients receive an additional two cycles of the VAH regimen. Upon achieving MRD negativity, they then proceed to the transplantation process.

The conditioning regimen includes fludarabine at 30 mg/m²/day from day -7 to day -3 (5 days), cytarabine at 1-1.5 g/m²/day from day -7 to day -3 (5 days), and busulfan at 3.2 mg/kg/day from day -5 to day -3 (3 days). Conditioning begins on day -6, and donor hematopoietic stem cell infusion is performed on day 0.

All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time.

The primary endpoint is the 1-year and 2-year overall survival (OS). Secondary endpoints include the complete response (CR) rate after 1 and 2 cycles of chemotherapy; 1-year and 2-year disease-free survival (DFS) following the achievement of CR through induction therapy; cumulative relapse rate; non-relapse mortality (NRM); incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant; and the cumulative incidence of chronic GVHD within 1 year and 2 years post-transplant.


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.

Primary outcomes:
measure: 1y and 2y-OS
timeFrame: up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai General hospital,Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Xianmin Song, MD
role: PRINCIPAL_INVESTIGATOR
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