NCT05870995

Chemotherapy CLAGE-Ven Sequential With Reduced Intensity Conditioning for Refractory Acute Myelodi Leukemia

A Phase II Single Arm Study of Cladribine, Cytarabine, Etoposide and Venetoclax Sequential With Reduced Dose Conditioning of Fludarabine, Busulfan and Melphalan or Total Marrow Radiation for Refractory Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Shanghai Jiao Tong University School of Medicine · Academic / Other
• Sex: All
• Age: 16 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The investigators developed a protocol combining chemotherapy of cladribine, cytarabine and etoposide (CLAGE) as debulking treatment sequential with reduced intensity conditioning regimen Flu-Bu to treat patients with refractory acute myeloid leukemia (AML). In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with modifications: 1) reduced dose of CLAGE; 2) Reduced intensity conditioning (RIC) regimen as fludarabine, busulfan and melphalan (MBF) or total marrow irradiation (TMI); 3) Venetoclax was added to the chemotherapy and conditioning regimen.

Detailed description

Refractory AML is associated with poor prognosis. Allogeneic stem cell transplantation is considered as the only curative therapy. Unfortunately, conventional transplantation protocol usually has high relapse rate and high nor-relapse mortality. In previous studies, the investigators established a protocol using intensive chemotherapy (cladribine, cytarabine and etoposide) to reduced the leukemia burden followed by reduced intensity conditioning regimen of Flu-Bu3 with 7 day interval. All patients received maintenance therapy. The 1-year relapse rate was less than 20% but toxicity such as lethal infection was documented in sizable part of patients. In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with following modifications: 1) dose of cytarabine and etoposide are reduced to 1g/m2 and 100mg/m2 daily; 2) conditioning regimen is based on Flu-Bu2 combined with addition of melphalan (100mg/m2) or total marrow irradiation (TMI) in case of contra-indication for busulfan or melphalan; 3) Venetoclax is added to the chemotherapy and conditioning regimen. The modifications intend to reduce both the toxicities and relapse, which may turn into a benefit of disease-free survival (DFS). This is designed as a phase II multi-center prospective study to evaluate the feasibility and efficacy of the protocol.

Conditions

• Refractory Leukemia

Interventions

Type	Name	Description
DRUG	CALGE-VEN- RIC-conditioning	Intensive chemotherapy Cladribine-cytarabine-etoposide -venetoclax sequential with fludarabine, busulfan and melphalan or fludarabine and total marrow irradiation

Timeline

• Start date: 2023-02-01
• Primary completion: 2026-02-01
• Completion: 2026-09-01
• First posted: 2023-05-23
• Last updated: 2025-02-18

Locations

3 sites across 1 country: China