Aza-Ven Followed by Reduced Toxicity Conditioning Regimen (MBF) as Salvage Therapy for Refractory AML.

Phase 2

• Conditions: Refractory Acute Myeloid Leukemia
• Interventions: Drug: Aza-Ven-allo-HSCT

• Registration Number: NCT04904237
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

In this phase clinical trail, we evaluate the efficacy and feasibility of azacytidine and venetoclax as leukemia debulking treatment followed by reduced intensity conditioning regimen consisting of Fludarabine + Busulfan + Melphalan as salvage treatment in patients with refractory AML .

Detailed Description

In refractory AML, allogeneic hematopoietic stem cell transplantation (allo-HCST) is considered as the only curative regimen. In this phase II clinical trial, we plan to evaluate the efficacy and feasibility of new sequential transplantation protocol. All patients receive azacytidine and venetoclax as leukemia debulking treatment which is followed by reduced intensity conditioning regimen consisting of Fludarabine (150mg/m2) + Busulfan (6.4mg/kg) + Melphalan (70mg/m2). The graft-versus host disease (GVHD) prophylaxis regimen is based on reduced dose of post-transplantation cyclophosphamide (PT-CY) 40mg/kg day+3\~+4, tacrolimus and low-dose anti-thymoglobulin (ATG, 2.5mg/kg) in case of HLA-matched unrelated donor or halo-donor transplantation.

Study Timeline

• Study Start: 2021-01-01
• Status Verified: 2021-05
• Study First Submitted: 2021-05-22
• Study First Submitted QC: 2021-05-22
• Study First Posted: 2021-05-27
• Last Update Submitted: 2021-05-27
• Last Update Posted: 2021-06-01
• Primary Completion: 2024-01-01
• Study Completion: 2024-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• refractory AML (no remission after 2 induction therapy, relapsed AML within 6 months of first complete remission (CR), relapse AML no CR after reinduction therapy), multiple relapse and refractory relapse AML
• patients with HLA matched related or unrelated donor (9~10/10) or haplo-identical related donor

Exclusion Criteria

• Patients with poor liver function (enzyme >2N or bilirubin >2N)
• poor renal function (Scr >1.5N)
• poor cardiac function （EF<45%）
• inform consent not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
aza-ven +MBF	Aza-Ven-allo-HSCT	treatment with aza-ven debulking therapy followed by allo-HSCT with MBF conditioning

Primary Outcome Measures

Name	Time	Method
relapse-free survival	12 months	event defined as relapse or death of any causes

Secondary Outcome Measures

Name	Time	Method
overall survival	12 months	event defined as death of all causes
non-relapse mortality	12 months	event defined as death of all causes other than leukemia relapse
relapse	12 months	event defined as leukemia relapse
GVHD and relapse free survival (GRFS)	12 months	event defined as leukemia relapse, death of any causes, III-IV aGVHD or moderate to severe cGVHD

Trial Locations

Locations (3)

Blood & Marrow Transplantation Center, RuiJin Hospital; 🇨🇳 Shanghai, China

Department of Hematology, Shanghai No6 Hospital; 🇨🇳 Shanghai, China

Shanghai ZhaXin Hospital; 🇨🇳 Shanghai, China