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

NCT03662087 | Unknown Phase 2

• 1 other identifier: HMA+DLI vs DLI-MRD-AL-2018
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Relapse

  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

  2 years

Secondary Outcomes (5)

• Disease-free survival (DFS)

  2 years

• Overall survival (OS)

  2 years

• Transplant-related mortality (TRM)

  2 years

• Incidence of acute GVHD

  100 days

• Incidence of chronic GVHD

  2 years

Study Arms (2)

HMA+DLI

EXPERIMENTAL

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AL patients who achieved CR at pre-transplantation undergoing allo-HSCT, DLI was not given and immunosuppressant were withdrawn if patients were MRD persistently negative.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 If patients were MRD positive by Day+30 post-transplantation, immunosuppressant were withdrawn.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

DLI

EXPERIMENTAL

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

Interventions

HMA+DLI COMBINATION_PRODUCT

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.

HMA+DLI

DLI BIOLOGICAL

DLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10\*8 mononuclear cells/kg.

DLI

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 22337715 BACKGROUND

MeSH Terms

Conditions

Neoplasm, Residual

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Qifa Liu

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hua Jin

CONTACT

+86-020-61641613; 499509173@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: September 5, 2018
• First Posted: September 7, 2018
• Study Start: October 1, 2018
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2022
• Last Updated: September 7, 2018

Record last verified: 2018-07

Locations

CN (1)