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

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).

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 .

Study Overview

• Status: Recruiting
• Conditions: Refractory Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Aza-Ven-allo-HSCT

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 Type: Interventional
• Enrollment (Anticipated): 23
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiong HU; Phone Number: 601878 86-21-64370045; Email: hj10709@rjh.com.cn
• Study Contact Backup: Name: Jie-ling Jiang; Phone Number: 601878 86-21-64370045; Email: jiangjieling66@hotmail.com

Study Locations

• China
  • Shanghai, China, 200025
    • Recruiting
    • Blood & Marrow Transplantation Center, RuiJin Hospital
  • Shanghai, China
    • Recruiting
    • Department of Hematology, Shanghai No6 Hospital
    • Contact: Chunkang Chang; Phone Number: 86-21-64369181; Email: changchunkang@sjtu.edu.cn
  • Shanghai, China
    • Recruiting
    • Shanghai ZhaXin Hospital
    • Contact: Chun Wang; Phone Number: 13386259777; Email: wangchun2@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Jiong HU, Shanghai Rui Jin Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2021
• Primary Completion (ANTICIPATED): January 1, 2024
• Study Completion (ANTICIPATED): June 1, 2024

Study Registration Dates

• First Submitted: May 22, 2021
• First Submitted That Met QC Criteria: May 22, 2021
• First Posted (ACTUAL): May 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: refractory; hematopoietic stem cell transplantation; acute myeloid leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: RJH-rAML-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No