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

NCT ID: NCT03793517

Last Updated: 2020-03-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2026-10-31

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 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.

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 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.

Conditions

Stem Cell Transplant Complications; Leukemia, Myeloid, Acute; Leukemia Relapse

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Decitabine plus mBU/CY for HLA-mismatched HSCT

Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD at the time of HLA-mismatched HSCT.

Details:

The conditioning therapy for human eukocyte 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, simustine (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.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Decitabine 200mg.m-2.d-1 intervanously on days -12 and -11

mBU/CY and ATG

Intervention Type: DRUG

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

Decitabine plus mBU/CY for matched sibling transplant

Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD 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, simustine (Me-CCNU, 250 mg/m2), orally once on day -3.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Decitabine 200mg.m-2.d-1 intervanously on days -12 and -11

mBU/CY

Intervention Type: DRUG

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

Interventions

Decitabine

Decitabine 200mg.m-2.d-1 intervanously on days -12 and -11

Intervention Type: 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 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

Intervention Type: 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 Simustine (Me-CCNU, 250 mg·m-2) orally once on day -3

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Huang,MD

Director of the Hematology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiao-Jun Huang

Role: STUDY_CHAIR

Peking University People's Hospital

Locations

Peking University Institute of Hematology,Beijing

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiao-Jun Huang

Role: CONTACT

yanchenhua@vip.sina.com

+86 010 88326666

Chen-Hua Yan

Role: CONTACT

yanchenhua@vip.sina.com

+86 010 88326666

Facility Contacts

Chen-hua Yan, MD

Role: primary

yanchenhua@vip.sina.com

86 010 88326666

Other Identifiers

decitabine pre-HSCT in MRD+ AL

Identifier Type: -

Identifier Source: org_study_id