Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia

Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia Patients Undergoing HSCT

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly causes of transplant failure. We reported previously that patients with relapse or refractory AL were at very high risk of relapse post allo-HSCT, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or refractory leukemia and myelodysplastic syndrome. It was reported that the combination of decitabine, with busulfan and cyclophosphamide as a preparative regimen for allo-HSCT using HLA-matching donors was safe and effective. In this prospective, single-arm clinical trial, we aimed to examine the efficacy of combining decitabine with modified busulfan and cyclophosphamide (mBU/CY) as a preparative regimen for allo-HSCT in recurrent and refractory AL patients.

Study Overview

• Status: Recruiting
• Conditions: Refractory Leukemia; Stem Cell Transplant Complications; Relapse Leukemia
• Intervention / Treatment: Drug: Decitabine; Drug: mBU/CY and ATG; Drug: mBU/CY

Detailed Description

Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG (thymoglobulin; Sang Stat, France) consisting of cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg·m-2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.

BM(bone marrow) samples from patients were obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 years after transplantation.

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University Institute of Hematology,Beijing
      • Contact: Jing Liu, MD; Phone Number: 86 010 88326666; Email: liujing0245@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with relapsed acute leukemia
• patients with acute leukemia in the third（or more）complete remission (CR3) status

Exclusion Criteria:

• pregnancy women
• uncontrolled severe infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Decitabine plus mBU/CY for HLA-mismatched HSCT; Decitabine plus mBU/CY as precondition regimen for recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT Details: The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2	Drug: Decitabine; Decitabine 200mg.m-2.d-1 intravenously on days -12 and -11; Drug: mBU/CY and ATG; Ara-C 4 g·m-2·d-1 intravenously on days -10 to -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Semustine (Me-CCNU, 250 mg·m-2) orally once on day -3 ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2
Experimental: Decitabine plus mBU/CY for matched sibling transplant; Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD (minimal residual disease) at the time of matched sibling transplant. Details: In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3.	Drug: Decitabine; Decitabine 200mg.m-2.d-1 intravenously on days -12 and -11; Drug: mBU/CY; hydroxycarbamide (80 mg·kg-1) orally on day -10 Ara-C (2 g·m-2·d-1) on day -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Semustine (Me-CCNU, 250 mg·m-2) orally once on day -3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year cumulative incidence of relapse	The cumulative incidence of relapse at 1 year post allo-HSCT	1 year post allo-HSCT
2 year cumulative incidence of relapse	The cumulative incidence of relapse at 2 years post allo-HSCT	2 years post allo-HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-relapse mortality	The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT	1 year post allo-HSCT
1 year overall survival	The overall survival at 1 year post allo-HSCT	1 year post allo-HSCT
1 year leukemia free survival	The leukemia free survival at 1 years post allo-HSCT	1 year post allo-HSCT
5 years leukemia free survival	The leukemia free survival at 5 years post allo-HSCT	5 years post allo-HSCT
engraftment	The total neutrophil and platelet engraftment rate	100 days post allo-HSCT
Acute graft versus host disease	The cumulative incidence of grade II-IV acute graft versus host disease	100 days post allo-HSCT
Chronic graft versus host disease	The cumulative incidence of intermediate to severe chronic graft versus host disease	1 years post allo-HSCT
5 years overall survival	The overall survival at 5 years post allo-HSCT	5 years post allo-HSCT] 1 year leukemia free survival

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: January 8, 2019
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 29, 2019
• Last Update Submitted That Met QC Criteria: May 27, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: allogeneic stem cell transplantation; refractory acute leukemia; recurrent acute leukemia; preconditioning regimen
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Recurrence; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: decitabine pre-HSCT for R/R AL

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