NCT06643962

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 83 (estimated)
• Sponsor: Affiliated Hospital of Nantong University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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).

Detailed description

This is a single-center, prospective cohort study for the intensifying treatment with venetoclax on the standard 3+7 regimen in newly diagnosed AML (non-APL) participants who have lower EPBCR based on ≦1.5log on day 4 of the 3+7 regimen. The key eligible criteria are newly diagnosed and treatment-naïve AML (non-APL) according to the WHO 2022 criteria. Participants are between 18 and 70 years old and fit for intensive chemotherapy. A leukemia-associated immunophenotype (LAIP) defined by multiparameter flow cytometry (MFC) according to the 2022 ELN recommendation (2022 ELN) is necessary for enrollment in this trial. All eligible participants receive the 3+7 regimen. Pretreatment with hydroxyurea is permitted to manage leukocytosis. LAIP+ cells are enumerated on EDTA-anticoagulated peripheral blood collected before chemotherapy on days 1 and 4 of the first induction cycle (each cycle is 28 days). At least 100 circulating LAIP+ cells per microliter on day 1 are required as inclusion criteria to ensure optimal sensitivity. The EPBCR is calculated on day 4 of the first induction regimen as a ratio converted to a logarithmic scale between the absolute peripheral blood LAIP+ cell count on day 1 (baseline) and day 4. A cut-off of 1.5 log is decisional to assign participants to treatment modalities. Participants with EPBCR\>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy. After two cycles of induction therapy, participants who fail to achieve composite complete remission (CR/CRi, CRc) may receive an alternative regimen per their physicians' decision. After CR/CRi is achieved, participants proceed with consolidation therapy or allo-HSCT based on their 2022 ELN risk categories. Participants with favorable risk should go through four cycles (each cycle is 28 days) of consolidation therapy, those with adverse risk should go through allogeneic hematopoietic stem cell transplantation (allo-HSCT) after two cycles of consolidation therapy, and those with intermediate risk can receive allo-HSCT after two cycles of consolidation therapy if suitable donors are available or continue with four cycles of consolidation therapy. Participants receive four cycles of consolidation regimen of intermediate-dose cytarabine for age \>60 years old or high-dose cytarabine for age \>60 years old. The consolidation therapy will be combined with venetoclax in the EPBCRlow cohort and not in the EPBCRhigh cohort. After consolidation, participants will receive maintenance therapy per their physicians' decision and be observed.

Conditions

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	Venetoclax	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.
DRUG	Idarubincin	Idarubicin (IDA): 10mg/m\^2/d (age \<60 years old) or 6mg/m\^2/d on days 1-3, intravenously (IV).
DRUG	Cytarabine	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.

Timeline

• Start date: 2024-10-31
• Primary completion: 2025-12-31
• Completion: 2027-10-31
• First posted: 2024-10-16
• Last updated: 2024-11-12

Locations

1 site across 1 country: China