Low Dose Decitabine + Modified BUCY Conditioning Regimen for High Risk Acute Myeloid Leukemia Undergoing Allo-HSCT

The purpose of this prospective, open-label, randomized multicenter study is to evaluate the safety and efficacy of low dose decitabine in combination with modified BUCY vs modified BUCY as a myeloablative conditioning regimen for high-risk patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT).

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation; Conditioning
• Intervention / Treatment: Drug: Decitabine plus Modified BUCY; Drug: Modified BUCY

Detailed Description

Allo-HSCT is the most effective treatment stratagey for high risk acute myeloid leukemia. At present, modified BUCY is the standard conditioning regimen for AML undergoing allo-HSCT in our institute. However, relapse occured in as high as 30-50% high risk AML patients after allo-HSCT. Thus, the best conditioning regimen for this subgroup remains to be optimized. Low dose decitabine in combination with chemotherapy have been shown to improve comple remission rate of high risk AML patients. To reduce the relapse rate after allo-HSCT, low dose decitabine is added in the modified BUCY regimen. In this study, the safety and efficacy of low dose decitabine + modified BUCY vs modified BUCY myeloablative conditioning regimens in high risk undergoing allo-HSCT are evaluated.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • the First Affiliated Hospital of Soochow University
      • Contact: Xiaowen Tang, MD; Phone Number: +86-512-67781851; Email: xwtang1020@163.com
      • Principal Investigator: Depei Wu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 12 to 60 years.
• Diagnosis of high-risk acute myeloid leukemia at the time of transplant. ("High-risk" AML features are defined by the following: relapsed or primary refractory AML; Secondary AML（AML Secondary to myelodysplastic syndrome(MDS) or treatment-related AML); extramedullary leukemia; adverse cytogenetic abnormalities of monosomy 5, monosomy 7, or deletion of 5q; or presence of FLT3 positive internal tandem duplication (FLT3/ITD+), particularly high allelic ratio.)
• Patient must have adequate pre-transplant organ function.

Exclusion Criteria:

• Age <12 or >60 years.
• Uncontrolled bacterial, viral, fungal, or other infection before conditioning regimen.
• Any other severe concurrent diseases, or have a history of serious organ dysfunction.
• Pregnant or lactating females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Decitabine plus Modified BUCY; For high-risk patients with Acute Myeloid Leukemia (AML) undergoing allo-HSCT, The Decitabine plus Modified BuCy regimen consisted of decitabine,semustine,cytarabine, busulfan and cyclophosphamide.	Drug: Decitabine plus Modified BUCY; Decitabine:20 mg/m²/day on day -14 to -10; Modified BUCY: Sibling:semustine 250 mg/m²/day on day -9;cytarabine 2 g/m²/day on day -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.; Unrelated:semustine 250 mg/m²/day on day -10;cytarabine 2 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.; Haploidentical:semustine 250 mg/m²/day on day -10;cytarabine 4 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.
Active Comparator: Modified BUCY; For high-risk patients with Acute Myeloid Leukemia (AML) undergoing allo-HSCT, The Modified BuCy regimen consisted of semustine,cytarabine, busulfan and cyclophosphamide.	Drug: Modified BUCY; Sibling:semustine 250 mg/m²/day on day -9;cytarabine 2 g/m²/day on day -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.; Unrelated:semustine 250 mg/m²/day on day -10;cytarabine 2 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.; Haploidentical:semustine 250 mg/m²/day on day -10;cytarabine 4 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free survival (DFS)	time from randomization to the first of reccurrence or death	3 year
overall survival (OS)	time from randomization to death from any cause	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
veno-occlusive disease (VOD)	incidence of veno-occlusive disease (VOD) events	3 year
graft-versus-host disease (GvHD)	incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD)	3 year
transplant related mortality （TRM）	cumulative incidence of transplant related mortality	3 year
relapse	cumulative incidence of relapse	3 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Southeast University, China; Jiangsu University; Xuzhou Medical University
• Investigators: Principal Investigator: Depei Wu, MD, the First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2017
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: May 21, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: August 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: DAC+BUCY

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No