G-CSF+DAC+BUCY vs G-CSF+DAC+BF Conditioning Regimen for High-risk MDS Undergoing Allo-HSCT

G-CSF+DAC+BUCY vs. G-CSF+DAC+BF Conditioning Regimen for Patients With High-risk MDS Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Allo-HSCT is the most effective way to cure high-risk MDS patients. At present, the best conditioning regimen for high-risk MDS patients undergoing allo-HSCT remains in discussion. In this prospective study, the safety and efficacy of G-CSF+DAC+BUCY and G-CSF+DAC+BF conditioning regimens in high-risk MDS patients undergoing allo-HSCT are evaluated.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndrome; Allogeneic Hematopoietic Stem Cell Transplantation; Conditioning
• Intervention / Treatment: Drug: Granulocyte Colony-Stimulating Factor(G-CSF); Drug: Decitabine (DAC); Drug: Fludarabine (FLU); Drug: Busulfan (BU); Drug: Busulfan; Drug: Cyclophosphamide (CY)

Detailed Description

Allo-HSCT is the most effective way to cure high-risk MDS patients. At present, the best conditioning regimen for high-risk MDS patients undergoing allo-HSCT remains in discussion. A previous study by the investigators has showed that G-CSF +DAC+BUCY conditioning regimen could reduce the relapse and improve the survival compared with BUCY conditioning regimen, while the two conditioning regimens both have high non-relapse mortality (NRM). Several retrospective and prospective studies have demonstrated that BF conditioning regimen has a lower NRM compared with BUCY conditioning regimen, while the relapse and survival are similar in patients undergoing BF and BUCY conditioning regimens. Based on the above, the investigators design the prospective randomized controlled study to evaluate the safety and efficacy of G-CSF+DAC+BUCY and G-CSF+DAC+BF conditioning regimens in high-risk MDS patients undergoing allo-HSCT.

• Study Type: Interventional
• Enrollment (Anticipated): 242
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology,Nanfang Hospital, Southern Medical University
      • Contact: Li Xuan; Phone Number: 15521251270; Email: 356135708@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Had a diagnosis of RAEB-1 or RAEB-2 with IPSS-R >3
• Age 18 to 65 years old
• ECOG performance status of 0-2
• HCT-CI of 0-2
• Were willing to undergo allo-HSCT

Exclusion Criteria:

• Therapy-related MDS
• Previous allo-HSCT
• Uncontrolled infections
• Liver or renal dysfunction
• Severe concomitant conditions not suitable for the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G-CSF+DAC+BF; For patients with high-risk MDS undergoing allo- HSCT, Granulocyte Colony-Stimulating Factor (G-CSF)+Decitabine+BF conditioning regimen was G-CSF 5ug/kg/day on days -17 to -10 (when white blood cell is more than 20G/L, stop using G-CSF), Decitabine 20mg/m2/day on days -14 to -10, Busulfan (BU) 3.2 mg/kg/day on days -6 to -3, Fludarabine (FLU) 30mg/m2/ day on days -7 to -3.	Drug: Granulocyte Colony-Stimulating Factor(G-CSF); G-CSF was administered at 5 ug/kg/day on days-17 to -10. When white blood cell is more than 20G/L, stop using G-CSF.; Drug: Decitabine (DAC); Decitabine was administered at 20mg/m2/day on days -14 to -10.; Drug: Fludarabine (FLU); Fludarabine was administered at 30 mg/m2/day on days -7 to -3.; Drug: Busulfan (BU); Busulfan was administered at 3.2 mg/kg/day on days -6 to -3 in G-CSF+DAC +BF group.
Active Comparator: G-CSF+DAC+BUCY; For patients with high-risk MDS undergoing allo- HSCT, Granulocyte Colony -Stimulating Factor (G-CSF)+Decitabine+BUCY conditioning regimen was G-CSF 5ug/kg/day on days -17 to -10 (when white blood cell is more than 20G/L, stop using G-CSF), Decitabine 20mg/m2/day on days -14 to -10, Busulfan (BU) 3.2 mg/kg/day on days -7 to -4, Cyclophosphamide (CY) 60 mg/kg/day on days -3, -2.	Drug: Granulocyte Colony-Stimulating Factor(G-CSF); G-CSF was administered at 5 ug/kg/day on days-17 to -10. When white blood cell is more than 20G/L, stop using G-CSF.; Drug: Decitabine (DAC); Decitabine was administered at 20mg/m2/day on days -14 to -10.; Drug: Busulfan; Busulfan was administered at 3.2 mg/kg/day on days -7 to -4 in G-CSF+DAC+BUCY group.; Drug: Cyclophosphamide (CY); Cyclophosphamide was administered at 60 mg/kg/day on days -3,-2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Non-relapse mortality (NRM)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	1 year
Cumulative incidence of relapse	1 year
Disease-free survival (DFS)	1 year
Adverse effects	within 100 days post-transplantation

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Peking University People's Hospital; Guangzhou First People's Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Institute of Hematology & Blood Diseases Hospital; First People's Hospital of Chenzhou; The Seventh Affiliated Hospital of Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: July 5, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Adjuvants, Immunologic; Cyclophosphamide; Decitabine; Lenograstim; Fludarabine; Busulfan
• Other Study ID Numbers: NFEC-2022-233

Drug and device information, study documents

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