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

Sponsor

Peking University People's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03799224

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stem Cell Transplant Complications Relapse Leukemia Refractory Leukemia	Drug: Decitabine Drug: mBU/CY and ATG Drug: mBU/CY	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model 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. 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 samples from patients would be 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 year after transplantation.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. 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 samples from patients would be 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 year after transplantation.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

1 year cumulative incidence of relapse [1 year post allo-HSCT]
The cumulative incidence of relapse at 1 year post allo-HSCT
2 year cumulative incidence of relapse [2 years post allo-HSCT]
The cumulative incidence of relapse at 2 years post allo-HSCT

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University Institute of Hematology,Beijing	Beijing	Beijing	China	100044

Sponsors and Collaborators

Peking University People's Hospital

Investigators

Study Chair: Xiao-Jun Huang, Peking University People's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Xiaojun Huang,MD, Director of the Hematology Department, Peking University People's Hospital

ClinicalTrials.gov Identifier:

NCT03799224

Other Study ID Numbers:

decitabine pre-HSCT for R/R AL

First Posted:

Jan 10, 2019

Last Update Posted:

May 29, 2019

Last Verified:

May 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Xiaojun Huang,MD, Director of the Hematology Department, Peking University People's Hospital

recurrent acute leukemia

refractory acute leukemia

preconditioning regimen

allogeneic stem cell transplantation

Additional relevant MeSH terms:

Leukemia

Recurrence

Decitabine

Study Results

No Results Posted as of May 29, 2019