Decitabine Plus mBU/CY for High Risk Acute Leukemia With MRD Pre-HSCT

Leukemia, Myeloid, Acute Clinical Trial

Official title:

Decitabine Plus mBU/CY for High Risk Acute Leukemia With Minimal Residual Disease Pre-HSCT

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03793517
• Other study ID #: decitabine pre-HSCT in MRD+ AL
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 1, 2018
• Est. completion date: October 2026

Study information

• Verified date: March 2020
• 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 high-risk molecular biomarkers who still have detectable minimal residual disease(MRD) pre-HSCT were at very high risk of relapse, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or refractory leukemia and myelodysplastiv syndrome. It was reported that the combination of decitabine, with busufan 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 patients with very high-risk AL and detectable MRD pre-HSCT.

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 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: October 2026
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• acute leukemia patients with MLL-r,TLS-ERG,or SIL-TAL1,whose minimal residual disease were detectable pre-HSCT

Exclusion Criteria:

• pregnancy women

• uncontrolled severe infection

Related Conditions & MeSH terms

• Leukemia
• Leukemia Relapse
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrence
• Stem Cell Transplant Complications

Intervention

Drug:
• Decitabine
Decitabine 200mg.m-2.d-1 intervanously 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 Simustine (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 Simustine (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
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