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

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ClinicalTrials.gov Identifier: NCT03793517
Recruitment Status : Recruiting
First Posted : January 4, 2019
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
Xiaojun Huang,MD, Peking University People's Hospital

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.

Condition or disease Intervention/treatment Phase
Stem Cell Transplant Complications Leukemia, Myeloid, Acute Leukemia Relapse Drug: Decitabine Drug: mBU/CY and ATG Drug: mBU/CY Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model 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. 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Decitabine Plus mBU/CY for High Risk Acute Leukemia With Minimal Residual Disease Pre-HSCT
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2026


Arm Intervention/treatment
Experimental: 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.

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

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

Experimental: 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.

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

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




Primary Outcome Measures :
  1. 1 year cumulative incidence of relapse [ Time Frame: 1 year post allo-HSCT ]
    The cumulative incidence of relapse at 1 year post allo-HSCT

  2. 2 year cumulative incidence of relapse [ Time Frame: 2 years post allo-HSCT ]
    The cumulative incidence of relapse at 2 years post allo-HSCT


Secondary Outcome Measures :
  1. Non-relapse mortality [ Time Frame: 1 year post allo-HSCT ]
    The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT

  2. 1 year overall survival [ Time Frame: 1 year post allo-HSCT ]
    The overall survival at 1 year post allo-HSCT

  3. 5 years overall survival [ Time Frame: 5 years post allo-HSCT ]
    The overall survival at 5 years post allo-HSCT

  4. 1 year leukemia free survival [ Time Frame: 1 year post allo-HSCT ]
    The leukemia free survival at 1 years post allo-HSCT

  5. 5 years leukemia free survival [ Time Frame: 5 years post allo-HSCT ]
    The leukemia free survival at 5 years post allo-HSCT

  6. engraftment [ Time Frame: 100 days post allo-HSCT ]
    The total neutrophil and platelet engraftment rate

  7. Acute graft versus host disease [ Time Frame: 100 days post allo-HSCT ]
    The cumulative incidence of grade II-IV acute graft versus host disease

  8. Chronic graft versus host disease [ Time Frame: 1 years post allo-HSCT ]
    The cumulative incidence of intermediate to severe chronic graft versus host disease



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03793517


Contacts
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Contact: Xiao-Jun Huang +86 010 88326666 yanchenhua@vip.sina.com
Contact: Chen-Hua Yan +86 010 88326666 yanchenhua@vip.sina.com

Locations
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China, Beijing
Peking University Institute of Hematology,Beijing Recruiting
Beijing, Beijing, China, 100044
Contact: Chen-hua Yan, MD    86 010 88326666    yanchenhua@vip.sina.com   
Principal Investigator: Xiao-Jun Huang, MD         
Sponsors and Collaborators
Peking University People's Hospital
Investigators
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Study Chair: Xiao-Jun Huang Peking University People's Hospital

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Responsible Party: Xiaojun Huang,MD, Director of the Hematology Department, Peking University People's Hospital
ClinicalTrials.gov Identifier: NCT03793517     History of Changes
Other Study ID Numbers: decitabine pre-HSCT in MRD+ AL
First Posted: January 4, 2019    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xiaojun Huang,MD, Peking University People's Hospital:
high risk acute myeloid leukemia
hematopoietic stem cell transplantation
leukemia relapse
preparation regimen
decitabine
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Recurrence
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Cyclophosphamide
Busulfan
Semustine
Decitabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors