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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Relapsed Adult ALL, Relapsed Adult AML

Intervention / Treatment
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* Drug: Plerixafor


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Plerixafor plus donor lymphocyte infusion for patients with relapsed acute leukemia
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plerixafor plus DLI<br>DLI will be given to the participants three days after chemotherapy, and plerixafor will be administrated ten days post DLI. | Drug: Plerixafor<br>* Plerixafor was injected subcutaneously to participants twice per day for five consecutive days ten days post DLI.<br>* Other names: AMD3100;|

What is the study measuring?
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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 |