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

NCT03793517 | Recruiting Phase 2

• 1 other identifier: decitabine pre-HSCT in MRD+ AL
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

high risk acute myeloid leukemia; hematopoietic stem cell transplantation; leukemia relapse; preparation regimen; decitabine

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Non-relapse mortality

  1 year post allo-HSCT

• 1 year overall survival

  1 year post allo-HSCT

• 5 years overall survival

  5 years post allo-HSCT

• 1 year leukemia free survival

  1 year post allo-HSCT

• 5 years leukemia free survival

  5 years post allo-HSCT

Study Arms (2)

Decitabine plus mBU/CY for HLA-mismatched HSCT

EXPERIMENTAL

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.

Drug: Decitabine; Drug: mBU/CY and ATG

Decitabine plus mBU/CY for matched sibling transplant

EXPERIMENTAL

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.

Drug: Decitabine; Drug: mBU/CY

Interventions

Decitabine DRUG

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

Decitabine plus mBU/CY for HLA-mismatched HSCT; Decitabine plus mBU/CY for matched sibling transplant

mBU/CY and ATG 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 HLA-mismatched HSCT

mBU/CY 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

Decitabine plus mBU/CY for matched sibling transplant

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• pregnancy women
• uncontrolled severe infection

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University Institute of Hematology,Beijing

Beijing, Beijing Municipality, 100044, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Xiao-Jun Huang

  Peking University People's Hospital

  STUDY CHAIR

Central Study Contacts

Xiao-Jun Huang

CONTACT

+86 010 88326666; yanchenhua@vip.sina.com

Chen-Hua Yan

CONTACT

+86 010 88326666; yanchenhua@vip.sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Hematology Department

Model Details: 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.

Study Record Dates

• First Submitted: December 23, 2018
• First Posted: January 4, 2019
• Study Start: September 1, 2018
• Primary Completion: October 1, 2023
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)