Venetoclax Combined with Intensive Therapy for Acute Myeloid Leukemia Patients with Lower Early Peripheral Blast Clearance Rate After Standard Induction Therapy
A Single-Center Prospective Cohort Study to Evaluate the Efficacy and Safety of Intensifying Treatment with Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (non-APL) and Exhibiting Lower Early Peripheral Blast Clearance Rate After Standard Intensive Induction Chemotherapy
Affiliated Hospital of Nantong University
83 participants
Oct 31, 2024
INTERVENTIONAL
Conditions
Summary
This single-center prospective cohort study aims to evaluate the efficacy and safety of Intensifying treatment with Venetoclax along with intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia (AML) except acute promyelocytic leukemia (non-APL) and exhibiting lower early peripheral blast clearance rate (EPBCR) after standard Intensive Induction therapy (3+7 regimen).
Eligibility
Inclusion Criteria15
- Newly diagnosed AML, except for the APL subtype, according to the 2022 World Health Organization classification (WHO 2022 criteria)
- Age ≥18 years and ≤70 years
- Eligible for intensive chemotherapy
- No prior chemotherapy for AML except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell \[WBC\] counts\>25x10\^9/L)
- Eastern Cooperative Oncology Group (ECOG) performance status≤2
- Adequate renal function is defined as:
- Serum creatinine≤2.0×upper limit of normal (ULN)
- Creatinine clearance (CrCl)\>30 mL/min calculated by the Cockcroft-Gault equation.
- Adequate hepatic and heart function is defined as:
- Serum total bilirubin≤1.5×ULN unless considered due to Gilbert's disease, or leukemic involvement
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)≤2.5×ULN, unless considered due to leukemic involvement
- Myocardial enzyme\<2.0×ULN
- Left ventricular ejection fraction is within the normal range by measure of echocardiogram (ECHO)
- Signed a written informed consent form (ICF)
- Female participants who are of non-reproductive potential (i.e., post-menopausal by history of no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female participants of childbearing potential must have a negative serum pregnancy test upon study entry
Exclusion Criteria25
- AML with BCR-ABL1 or myeloid blast crisis of CML
- Participants who have received prior treatment for AML with chemotherapy, hypomethylating agents, or venetoclax
- Participants who are ineligible for intensive induction chemotherapy:
- ≧71 years old OR
- ≧18 to 70 years old and fulfill at least one criterion associated with lack of fitness for intensive induction chemotherapy:
- ECOG PS of 2-3
- Cardiac history of CHF requiring treatment or Ejection Fraction ≦50% or chronic stable angina
- Diffusing capacity of the lungs for carbon monoxide (DLCO)≦65% or the forced expiratory volume in one second (FEVI) ≦65%
- Participants with a prior history of MDS, MPN, or MDS/MPN
- Participants with other concurrent malignant tumors on treatment, except for:
- Malignancy treated with curative intent and with no known active disease present for ≧3 years
- Adequately treated non-melanoma skin cancer or lentigo maligna without current evidence of disease
- Adequately treated carcinoma in situ without current evidence of disease
- Localized prostate cancer with a Gleason score of 6 or less
- Pregnant or lactating women
- Active heart disease is defined as any one of the following:
- Uncontrolled or symptomatic angina pectoris
- A myocardial infarction six months before enrolled
- Arrhythmia needs medication or with severe clinical symptoms
- Uncontrolled or symptomatic congestive heart failure (New York Hear Association \[NYHA\] classification\> grade 2)
- Participants with an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
- Participants with an active viral infection caused by HIV, hepatitis B, or hepatitis C virus that cannot be controlled by treatment
- Participants with evidence of central nervous system leukemia before the study treatment
- Participants with epilepsy which needs drug treatment, dementia, or other abnormal mental states that prevent understanding or following the protocol
- Conditions that restrict the intake or absorption of orally administered drugs
Interventions
Venetoclax in the EPBCRlow cohort will be added to the ongoing 3+7 regimen. In the first induction cycle: venetoclax needs to be ramped up: 100 mg on day 5, 200mg on day 6, and 400mg on days 7-14, orally once daily. In the second induction (if required), venetoclax 400mg will be administered orally once daily on days 5-14 without a dose ramp-up schedule. Venetoclax in the EPBCRlow cohort during consolidation therapy: 400mg on days 1-7, orally once daily, along with the consolidation chemotherapy.
Idarubicin (IDA): 10mg/m\^2/d (age \<60 years old) or 6mg/m\^2/d on days 1-3, intravenously (IV).
During induction therapy: 100mg/m2/d on days 1-7, IV. During consolidation therapy: intermediate-dose cytarabine for age \>55 years old: 1.0g/m\^2 q12h on days 1-3, high-dose cytarabine for age ≦55 years old: 2g/m2 q12h on days 1-3.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT06643962