Fractionated Busulfan Conditioning Regimen for Allo-HSCT in Non-remission Myeloid Malignancies

Fractionated Busulfan Combined With Chidamide/Fludarabine/Cytarabine (ChiFAB) With Allogeneic Hematopoietic Stem-Cell Transplantation in Non-remission Myeloid Malignancies: a Phase II Study

The goal of this single-arm phase II study is to test in patients with non-remission myeloid malignancies undergoing allogeneic hemopoietic stem-cell transplantation (allo-HSCT). The main question it aims to answer are:

• The safety and efficacy of fractionated busulfan Combined With Chidamide/Fludarabine/Cytarabine(ChiFAB) conditioning regimen in increasing the overall survival rate in patients with non-remission myeloid malignancies after allo-HSCT.
• The efficacy of fractionated busulfan conditioning regimen in reducing the recurrence rate in patients with non-remission myeloid malignancies after allo-HSCT.

Participants will receive fractionated busulfan-based ChiFAB conditioning regimen (busulfan 3.2mg/kg d-13, -12, 1.6mg/kg d-6~-3, fludarabine 35mg/m2 d-6~-2, cytarabine 1g/m2,d-6~-2, chidamide 30mg d-13,-10,-6,-3) before allo-HSCT.

Study Overview

• Status: Recruiting
• Conditions: Myeloid Malignancies
• Intervention / Treatment: Drug: fractionated busulfan-based conditioning regimen

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chendu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Jie Ji, MD; Phone Number: 86-28-85422370; Email: jijie@wchscu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old and ≤ 65 years old when signing the Informed Consent Form (ICF);
2. KPS score > 60 or ECOG score 0-2;
3. The expected survival period > 3 months;
4. Those who did not achieve complete remission after 2 or more chemotherapy regimens. The proportion of blasts on bone marrow smears before transplantation was ≥5%.
5. Those who have no central nervous system involvement or serious functional damage to important organs of the body;
6. Fully understand and be informed of this study and sign the ICF; willing to follow and have the ability to complete all test procedures;

Exclusion Criteria:

1. Serious basic diseases of important organs: such as myocardial infarction, chronic cardiac insufficiency, decompensated hepatic insufficiency, renal function, gastrointestinal insufficiency, etc.;
2. Uncontrolled active infection (including bacterial, fungal, or viral infection), and drug treatment is ineffective;
3. Participating in other clinical studies, or planning to start treatment in this study and less than 4 weeks before the end of treatment in the previous clinical study;
4. Combined with other malignant tumors and require treatment;
5. Pregnant or lactating females;
6. Patients with known history of human immunodeficiency virus (HIV) virus infection and/or acquired immunodeficiency syndrome;
7. Patients with active chronic hepatitis B or active hepatitis C;
8. History of prolonged QT syndrome;
9. Patients considered by other researchers to be unsuitable for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: fractionated busulfan; fractionated busulfan-based ChiFAB conditioning regimen: busulfan 3.2mg/kg d-13, -12, 1.6mg/kg d-6~-3, fludarabine 35mg/m2 d-6~-2 cytarabine 1g/m2,d-6~-2 chidamide 30mg d-13,-10,-6,-3

Drug: fractionated busulfan-based conditioning regimen; Drug: Chidamide 30 mg oral twice weekly for 2 weeks Drug: Fludarabine 35 mg/m2 intravenously daily for 5 days in the 2nd week Drug: Cytarabine 1 g/m2 intravenously for 5 days in the 2nd week Drug: Busulfan 3.2 mg/kg intravenously daily for 2 days in the 1st week, 1.6 mg/kg intravenously daily for 4 days in the 2nd week Procedure/Surgery: allogeneic hematopoietic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival of this group of patients at the end of 2 year	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse rate	Relapse rate of this group of patients at the end of 2 year	2 years
Cumulative incidence of acute graft versus host disease (aGVHD)	Cumulative incidence of acute graft versus host disease (aGVHD) of this group of patients at day+100	Day +100
Cumulative incidence of chronic graft versus host disease (cGVHD)	Cumulative incidence of chronic graft versus host disease (cGVHD) of this group of patients at the end of 2 year	2 years
Non-relapse mortality (NRM)	Non-relapse mortality of this group of patients at the end of 6 months	6 months

Collaborators and Investigators

• Sponsor: Sichuan University

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2023
• Primary Completion (Anticipated): August 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: March 29, 2023
• First Submitted That Met QC Criteria: March 29, 2023
• First Posted (Actual): April 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: allo-HSCT; myeloid malignancies
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Busulfan
• Other Study ID Numbers: Fra-Bu 1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Release after the publication of results of this trial
• IPD Sharing Time Frame: after the publication of results of this trial
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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