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

Phase 2

• Conditions: Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Cell Transplantation
• Interventions: Biological: DLI; Combination Product: HMA+DLI

• Registration Number: NCT03662087
• Lead Sponsor: Nanfang Hospital, 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.

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.

Study Timeline

• Status Verified: 2018-07
• Study First Submitted: 2018-09-05
• Study First Submitted QC: 2018-09-05
• Last Update Submitted: 2018-09-05
• Study First Posted: 2018-09-07
• Last Update Posted: 2018-09-07
• Study Start: 2018-10
• Primary Completion: 2021-10
• Study Completion: 2022-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DLI	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.
HMA+DLI	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.

Primary Outcome Measures

Name	Time	Method
Relapse	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

Name	Time	Method
Incidence of chronic GVHD	2 years	Chronic GVHD was assessed in patients alive after day 100
Disease-free survival (DFS)	2 years	DFS was defined as the time from transplantation to relapse or death in remission
Overall survival (OS)	2 years	OS was defined as the time from transplantation to death from all causes
Transplant-related mortality (TRM)	2 years	TRM was defined as death from any cause except relapse
Incidence of acute GVHD	100 days	Acute GVHD was graded according to standard criteria

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China