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

Stem Cell Transplant Complications Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03799224
• Other study ID #: decitabine pre-HSCT for R/R AL
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 1, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2019
• Source: Peking University People's Hospital
• Contact: Xiao-Jun Huang
• Phone: +86 010 88326666
• Email: yanchenhua[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Recurrence
• Refractory Leukemia
• Relapse Leukemia
• Stem Cell Transplant Complications

Intervention

Drug:
• Decitabine
Decitabine 200mg.m-2.d-1 intravenously on days -12 and -11
• 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
• 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

Locations

Country	Name	City	State
China	Peking University Institute of Hematology,Beijing	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1 year cumulative incidence of relapse	The cumulative incidence of relapse at 1 year post allo-HSCT	1 year post allo-HSCT
Primary	2 year cumulative incidence of relapse	The cumulative incidence of relapse at 2 years post allo-HSCT	2 years post allo-HSCT
Secondary	Non-relapse mortality	The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT	1 year post allo-HSCT
Secondary	1 year overall survival	The overall survival at 1 year post allo-HSCT	1 year post allo-HSCT
Secondary	5 years overall survival	The overall survival at 5 years post allo-HSCT	5 years post allo-HSCT] 1 year leukemia free survival
Secondary	1 year leukemia free survival	The leukemia free survival at 1 years post allo-HSCT	1 year post allo-HSCT
Secondary	5 years leukemia free survival	The leukemia free survival at 5 years post allo-HSCT	5 years post allo-HSCT
Secondary	engraftment	The total neutrophil and platelet engraftment rate	100 days post allo-HSCT
Secondary	Acute graft versus host disease	The cumulative incidence of grade II-IV acute graft versus host disease	100 days post allo-HSCT
Secondary	Chronic graft versus host disease	The cumulative incidence of intermediate to severe chronic graft versus host disease	1 years post allo-HSCT