MRD-directed Donor Lymphocyte Infusion for Reduce of Relapse After Allo-HSCT

Minimal Residual Disease-directed Donor Lymphocyte Infusion for Reduce of Relapse After Allogenetic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse remains an important problem. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI), and another transplantation used alone or in combination. However, the efficacy of these interventions is limited. One approach to the relapse problem is to intervene before hematologic or pathologic relapse occurs based on minimal residual disease (MRD). In this study, the efficacy of MRD-directed DLI on transplantation outcomes will be evaluated in patients with acute leukemia receiving allo-HSCT.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Stem Cell Transplantation; Minimal Residual Disease; Relapse; Donor Lymphocyte Infusion
• Intervention / Treatment: Biological: donor lymphocyte infusion

Detailed Description

Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse remains an important problem. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI), and another transplantation used alone or in combination. However, the efficacy of these interventions is limited. One approach to the relapse problem is to intervene before hematologic or pathologic relapse occurs based on minimal residual disease (MRD) using immune or molecular techniques.DLI is an effective post-transplantation therapy for prophylaxis of leukemia relapse, but is associated with a substantial risk of GVHD. Whether MRD-directed DLI could improve outcomes remains unclear. In this study, the efficacy of MRD-directed DLI on transplantation outcomes will be evaluated in patients with acute leukemia receiving allo-HSCT.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with acute leukemia
• receiving allo-HSCT

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MRD-directed DLI; For patients with MRD+ and without grade II/>II aGVHD by day +60 post-transplantation, DLI was given once by day +60 and was then administered based on MRD and GVHD status. If patients were MRD negative, DLI was not given again; if patients were MRD positive and without GVHD, DLI was given monthly until GVHD occurred or MRD became negative or for a total of four times. For patients with NR or PR pre-transplantation and with MRD negative by day +60 post-transplantation, DLI was given once by day +90 regardless of MRD, and was then administered when MRD became positive. For patients with CR pre-transplantation and with MRD negative post-transplantation, DLI was not given unless MRD became positive.

Biological: donor lymphocyte infusion; DLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10*8 mononuclear cells/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
relapse rate	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	1 year
disease-free survival	1 year

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Peking University People's Hospital; Guangzhou First People's Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Zhujiang Hospital; Third Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, Han W, Wang Y, Qin YZ, Huang XJ. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 2012 Apr 5;119(14):3256-62. doi: 10.1182/blood-2011-09-380386. Epub 2012 Feb 14.
• Fan M, Wang Y, Lin R, Lin T, Huang F, Fan Z, Xu Y, Yang T, Xu N, Shi P, Nie D, Lin D, Jiang Z, Wang S, Sun J, Huang X, Liu Q, Xuan L. Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia. Chin Med J (Engl). 2022 Apr 20;135(8):930-939. doi: 10.1097/CM9.0000000000001852.
• Yu S, Huang F, Fan Z, Xuan L, Nie D, Xu Y, Yang T, Wang S, Jiang Z, Xu N, Lin R, Ye J, Lin D, Sun J, Huang X, Wang Y, Liu Q. Haploidentical versus HLA-matched sibling transplantation for refractory acute leukemia undergoing sequential intensified conditioning followed by DLI: an analysis from two prospective data. J Hematol Oncol. 2020 Mar 12;13(1):18. doi: 10.1186/s13045-020-00859-5.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): October 25, 2018
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: January 23, 2016
• First Submitted That Met QC Criteria: January 30, 2016
• First Posted (Estimate): February 3, 2016

Study Record Updates

• Last Update Posted (Actual): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplastic Processes; Recurrence; Neoplasm, Residual
• Other Study ID Numbers: MRD-directed DLI-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No