Plerixafor Plus Donor Lymphocyte Infusion for Relapsed Acute Leukemia After Allo-HSCT

A Single Arm Study of Using Plerixafor Plus Donor Lymphocyte Infusion in the Treatment of Patients With Relapsed Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Acute leukemia, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), is the subtype of leukemia with the highest mortality, and leukemia relapse caused by the protective bone marrow microenvironment is the main cause of treatment failure. The chemokine receptor CXCR4 plays a crucial role in the homing and settling of leukemia cells into the bone marrow. Preclinical study of the investigators demonstrates that CXCR4 blockade can mobilize leukemia cells from their protective bone marrow microenvironment to periphery, thereby significantly enhancing the killing effect of allogeneic lymphocytes against leukemia cells. This study aims to preliminarily evaluate the efficacy and safety of donor lymphocyte infusion (DLI) plus CXCR4 antagonist plerixafor in the treatment of relapsed acute leukemia patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) through a prospective single arm study. The results may preliminarily confirm the effectiveness and safety of DLI combined with plerixafor in the treatment of recurrent acute leukemia patients after allo-HSCT, providing a reference basis for further research.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed Adult AML; Relapsed Adult ALL
• Intervention / Treatment: Drug: Plerixafor

Detailed Description

Patients with relapsed acute leukemia post allo-HSCT will be screened for the eligibility of this clinical trial. The participants will receive chemotherapy to reduce leukemia burden followed by DLI three days later. Ten days post DLI, plerixafor will be administrated to the participants (subcutaneous injection, twice per day) for a consecutive five days. The second round of DLI plus plerixafor will be given if the participants achieving partial remission or complete remission with positive minimal measurable disease. Short-term responses and long-term outcomes will be evaluated and safety of this therapeutic regimen will be assessed.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The age of the patients is ≥ 14 and ≤ 60 years old;
• Those with relapsed acute leukemia after allo-HSCT with bone marrow blasts less than 50%;
• The expected survival exceeds 3 months;
• At least 100 days post transplantation, and the immunosuppressants were discontinued;
• Those with no significant abnormalities of the main organ function: creatinine ≤ 176.8 μ Mol/L, bilirubin ≤ 51.3 μ Mol/L, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the normal upper limit;
• Sign an informed consent form.

Exclusion Criteria:

• Those with patient-specific human leukocyte antigen (HLA) loss at relapse;
• Those with active graft-versus-host disease;
• Those with severe infection;
• Those with organ function failure;
• Those with an Eastern Cooperative Oncology Group (ECOG) score more than 2 points;
• Those who are allergic to experimental drugs;
• Those who use other anti-leukemia therapies, such as radiotherapy, cellular immunotherapy, or Chinese medical herbs;
• Those participate in other clinical trials simultaneously;
• Those having mental illness or other illnesses that cannot fully comply with treatment or follow-up requirements;
• Those with extramedullary leukemia;
• Those with other conditions that researchers evaluate who are not proper to participate in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Plerixafor plus DLI; DLI will be given to the participants three days after chemotherapy, and plerixafor will be administrated ten days post DLI.	Drug: Plerixafor; Plerixafor was injected subcutaneously to participants twice per day for five consecutive days ten days post DLI.; Other Names: AMD3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission rates of the enrolled participants	The remission rates of the participants include complete remission rate, partial remission rate, and overall response rate.	Three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS) of the enrolled participants	DFS is defined from achievement of complete remission to disease relapse.	Twelve months
Overall survival of the enrolled participants	DFS is defined from enrollment to death, last contact, or end of this clinical trial.	Twelve months
Number of participants with acute and chronic graft-versus-host disease (GVHD)	Any grade of acute and chronic GVHD of the participants will be recorded. The acute GVHD will be assessed by MAGIC guidelines and chronic GVHD will be assessed by National Comprehensive Cancer Network (NCCN) guidelines.	Twelve months
Number of participants with non-relapse mortality	Non-relapse mortality (NRM) is defined as any cause of death without leukemia relapse.	Twelve months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Treatment-related adverse events will be assessed by CTCAE v5.0, including hematological and non-hematological adverse events. However, the occurrence of GVHD is not included.	One month after treatment

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University
• Investigators: Study Director: Long Su, PhD, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 19, 2023
• First Posted (Estimated): November 21, 2023

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 19, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: MLEU

Drug and device information, study documents

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