NCT04824924

A Phase 2 Study of Venetoclax in Combination With Low-dose HHT, G-CSF, and AZA as First-line Treatment for Newly Diagnosed Elderly AML Patients Unfit for Intensive Chemotherapy

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Shanghai Jiao Tong University School of Medicine · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

Acute myeloid leukemia (AML) is a group of heterogeneous malignancies derived from hematopoietic precursors. Patients older than 65 years can hardly benefit from standard intensive chemotherapy while having a poor toxicity tolerance, leading to a dismal prognosis. Currently, there is no satisfactory treatment modality for this high-risk patient population, which is an unmet clinical need. Venetoclax (ABT-199/GDC-0199, VEN) is a highly selective, oral B-cell lymphoma 2 (BCL-2) inhibitor that has shown activity in BCL-2- dependent leukemia and lymphoma cell lines, and has recently exerted encouraging therapeutic effect with manageable toxicity profile in the field of treatment of AML. Promising results have emerged in the combination of venetoclax and hypomethylating agents (HMA), decitabine or azacitidin (AZA), producing complete remission (CR) plus CR with incomplete hematologic recovery (CRi) rates of 74% and 66.7%, respectively, in previously untreated elderly AML patients. Homoharringtonine (HHT) is an alkaloid and has been used in Chinese patients with acute and chronic myeloid leukemia for more than 30 years. The add of HHT to the combination of cytarabin and aclarubicin or daunorubicin has been proved to improve CR rate and prognosis of AML patients. Moreover, HHT combined with low-dose cytarabine and granulocyte colony-stimulating factor (G-CSF) has achieved durable efficacy in AML patients, either in the first-line or salvage setting. Interestingly, HHT has potent synergistic effects with VEN through reducing the expression of BCL-XL and MCL-1 in BCL-2 related pathways as previouly reported. This study aims at investigating the combination of HHT, VEN, AZA and G-CSF (HVAG) in the treatment of newly diagnosed elderly AML patients who are ineligible for intensive chemotherapy.

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	The combination of HHT, venetoclax, AZA, G-CSF	HVAG regimen in a 28-day cycle HHT: d1-d7 1mg/m2; VEN: d1 100mg, d2 200mg, d3-d28 400mg; AZA: d1-d7 75mg/m2; G-CSF: d1-d7 300mg

Timeline

• Start date: 2021-03-01
• Primary completion: 2024-03-01
• Completion: 2024-03-01
• First posted: 2021-04-01
• Last updated: 2021-04-01