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

Study Overview
=================
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.

Official Title
-----------------
Azacytidine-venetoclax Combination as Leukemia Debulking Treatment Followed by Reduced Toxicity Conditioning Regimen (Melphalan Busulfan and Fludarabine, MBF) as Salvage Therapy for Refractory Acute Myeloid Leukemia (AML).

Conditions
-----------------
Refractory Acute Myeloid Leukemia

Intervention / Treatment
-----------------
* Drug: Aza-Ven-allo-HSCT


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aza-ven +MBF<br>treatment with aza-ven debulking therapy followed by allo-HSCT with MBF conditioning | Drug: Aza-Ven-allo-HSCT<br>* aaa-ven treatment followed by allo-HCTS with reduced toxicity conditioning (RTC) of Fludarabine, Busulifan and Melphalan<br>* Other names: Aza-Ven MBF;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse-free survival | event defined as relapse or death of any causes | 12 months | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
refractory, acute myeloid leukemia, hematopoietic stem cell transplantation