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HMA+DLI vs DLI Preemptive Therapy Based on MRD for AL Undergoing Allo-HSCT

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ClinicalTrials.gov Identifier: NCT03662087
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
Qifa Liu, Nanfang Hospital of Southern Medical University

Brief Summary:
Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse is the most common problem affecting long-term survivors of allo-HSCT. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI) or combination therapy. In this prospective randomized controlled study, the safety and efficacy of hypomethylating agents (HMA) + DLI and DLI preemptive therapy based on minimal residual disease in acute leukemia undergoing allo-HSCT are evaluated.

Condition or disease Intervention/treatment Phase
Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Cell Transplantation Combination Product: HMA+DLI Biological: DLI Phase 2 Phase 3

Detailed Description:
Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse is the most common problem affecting long-term survivors of allo-HSCT. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI) or combination therapy. One method of solving relapse is to intervene before hematologic or pathologic relapse occurs based on minimal residual disease (MRD) . DLI is an effective post-transplantation therapy based on MRD for relapse. Whether combination of hypomethylating agents (HMA) and DLI could improve outcomes remains unclear. In this prospective randomized controlled study, the safety and efficacy of HMA+DLI and DLI preemptive therapy based on minimal residual disease in acute leukemia undergoing allo-HSCT are evaluated.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hypomethylating Agents + Donor Lymphocyte Infusion vs Donor Lymphocyte Infusion Preemptive Therapy Based on Minimal Residual Disease for Acute Leukemia Undergoing Allogenetic Hematopoietic Stem Cell Transplantation
Estimated Study Start Date : October 2018
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: HMA+DLI
For AL patients who achieved CR at pre-transplantation undergoing allo-HSCT, DLI was not given and immunosuppressant were withdrawn if patients were MRD persistently negative. MRD status were monitored every 30 days. If patients were MRD negative by Day+30 post-transplantation, MRD status would be continued to be monitored by Day+60. If patients were MRD positive by Day+30 post-transplantation, immunosuppressant were withdrawn. If MRD were persistently positive until Day+60 or MRD changed from negative by Day+30 to positive by Day +60 post-transplantation, HMA and DLI were given. DLI was given 48 hours after administration of HMA. DLI was given monthly until GVHD occurred or MRD became negative or a total of four times. If MRD changed from positive by Day+30 to negative by Day+60 post-transplantation, MRD status would be continued to be monitored by Day+90 post-transplantation. If patients were MRD positive by Day+90 post-transplantation, HMA and DLI were given as shown above.
Combination Product: HMA+DLI
HMA: Decitabine was administered at 20mg/m2/day for five consecutive days or Ara-C was administered at 75mg/m2/day for seven consecutive days. DLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10*8 mononuclear cells/kg.

Experimental: DLI
For AL patients who achieved CR at pre-transplantation undergoing allo-HSCT, DLI was not given and immunosuppressant were withdrawn if patients were MRD persistently negative. MRD status were monitored every 30 days. If patients were MRD negative by Day+30 post-transplantation, MRD status would be continued to be monitored by Day+60 post-transplantation. If patients were MRD positive by Day+30 post-transplantation, immunosuppressant were withdrawn. If MRD were persistently positive until Day+60 or MRD changed from negative by Day+30 to positive by Day+60 post-transplantation, DLI was given. DLI was given monthly until GVHD occurred or MRD became negative or a total of four times. If MRD changed from positive by Day+30 to negative by Day+60 post-transplantation, MRD status would be continued to be monitored by Day+90 post-transplantation. If patients were MRD positive by Day+90 post-transplantation, DLI was given as shown above.
Biological: DLI
DLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10*8 mononuclear cells/kg.




Primary Outcome Measures :
  1. Relapse [ Time Frame: 2 years ]
    Relapse was defined by reappearance of blasts in the peripheral blood, recurrence of BM blasts >5%, or development of extramedullary disease infiltrates at any site


Secondary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: 2 years ]
    DFS was defined as the time from transplantation to relapse or death in remission

  2. Overall survival (OS) [ Time Frame: 2 years ]
    OS was defined as the time from transplantation to death from all causes

  3. Transplant-related mortality (TRM) [ Time Frame: 2 years ]
    TRM was defined as death from any cause except relapse

  4. Incidence of acute GVHD [ Time Frame: 100 days ]
    Acute GVHD was graded according to standard criteria

  5. Incidence of chronic GVHD [ Time Frame: 2 years ]
    Chronic GVHD was assessed in patients alive after day 100



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Ages Eligible for Study:   14 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- A patient age of 14-65 years. AL patients who achieved CR at pre-transplantation undergoing allo-HSCT. Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

  • AL patients who were in NR at pre-transplantation undergoing allo-HSCT. Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure). Patients with any conditions not suitable for the trial (investigators' decision).

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): NCT03662087


Contacts
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Contact: Hua Jin +86-020-61641613 499509173@qq.com

Locations
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China, Guangdong
Department of Hematology,Nanfang Hospital, Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Hua Jin    +86-020-61641613    499509173@qq.com   
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
Investigators
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Principal Investigator: Qifa Liu Nanfang Hospital of Southern Medical University
Publications:
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Responsible Party: Qifa Liu, Prof., Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT03662087    
Other Study ID Numbers: HMA+DLI vs DLI-MRD-AL-2018
First Posted: September 7, 2018    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Neoplasm, Residual
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Neoplastic Processes