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

NCT03799224 | Unknown Phase 2

• 1 other identifier: decitabine pre-HSCT for R/R 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 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.

Conditions

Stem Cell Transplant Complications; Relapse Leukemia; Refractory Leukemia

Keywords

recurrent acute leukemia; refractory acute leukemia; preconditioning regimen; allogeneic stem cell transplantation

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 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 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; 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 (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; Drug: mBU/CY

Interventions

Decitabine DRUG

Decitabine 200mg.m-2.d-1 intravenously 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 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

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 Semustine (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:

• patients with relapsed acute leukemia
• patients with acute leukemia in the third（or more）complete remission (CR3) status

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

Interventions

Decitabine

Condition Hierarchy (Ancestors)

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: January 8, 2019
• First Posted: January 10, 2019
• Study Start: December 1, 2018
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2023
• Last Updated: May 29, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)