Interferon-α Prevents Leukemia Relapse of AML Patients After Transplantation

Study Overview
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Brief Summary
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Allogeneic stem cell transplantation (SCT) remains a powerful therapeutic modality for patients with acute myeloid leukemia (AML).The superior clinical outcomes of allogeneic human SCT versus chemotherapy alone as post-remission treatment could be related to the graft-versus-leukemia (GVL) effects of recovered donor T cells. Our previous study investigated both the association of MRD status with transplant outcomes in haplo-SCT and matched sibling donor transplantation(MSDT)， and also possible differences in the transplant outcomes of patients with positive pre-MRD (as determined by MFC) who underwent haplo-SCT versus MSDT. It provided new evidence that unmanipulated haplo-SCT is superior to matched sibling donor transplantation in eradicating pre-transplantation MRD, indicating that unmanipulated haploidentical allografts have stronger GVL effects.As to the AML patients in standard-risk, who have a positive MRD before MSDT, whether these patients should be given any relapse prevention is the question to be answered in this study. Interferon α-2b exerts a relatively strong immunomodulatory effect. It can kill AL cells by regulating T-cell and/or natural killer cell functions.Consequently, interferon α-2b may have potential value for high-risk AL patients after transplantation. The study hypothesis: Using interferon α-2b following hematopoietic stem cell transplantation in patients with standard-risk AML can further reduce relapse rate and improve leukemia-free survival.

Detailed Description
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The standard-risk AML patients (18-60 years) receiving HLA-identical allogeneic stem cell transplantation in Peking University Institute of Hematology will be enrolled in this study if their MRD were positive before SCT, in CR1/CR2, remain in CR and MRD negative in the first two months after transplantation. The patients in this study will be treated with interferon-alpha injection twice a week (3 million units / time, iH) since the third month posttransplant. If the patients were well tolerated, the interferon-alpha treatment will continue 6 months. All the enrolled patients will undergo MRD monitoring after SCT as the same as the routine procedure. Bone marrow examination will be performed at the regular time points (+1, 2,3, 4, 5, 6, 9, 12 month) and 8-colour flow cytometry and RQ-PCR-based WT1 examination will be empolyed to evaluate MRD and disease status. Based on the statistical calculation, in order to reduce the incidence of relapse from 40% (previous data) to 15% (the cumulative incidence of relapse in pre-MRD- AML patients), total 29 patients will be enrolled. The main side effects might related to interferon-alpha include induction of severe GVHD, hematological toxicity and Flu - like symptoms. If the patients met the following criteria, they will withdraw from the trial: 1）met the combined criteria for positive MRD (MRDco+) which was defined as 2 consecutive FCM+ or WT1+ results or both FCM+ and WT1+ in a single sample within 1 year after transplantation; 2）hematological relapse; 3) grade III or IV acute GVHD, or moderate/ severe chronic GVHD; 4) severe infection; 5) grade IV hematological toxicity; 6) organ failure; 7) death; 8) patients refuse to continue the interferon-alpha treatment. The main end point of the study is one-year cumulative incidence of relapse. the second end points include OS, NRM, DFS, MRD, GVHD, infection and hematological toxicity.

Official Title
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Interferon-α Prevents Leukemia Relapse of AML Patients Undergoing HLA-identical Allogeneic Hematopoietic Stem Cell Transplantation With Pretransplant MRD

Conditions
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Relapse, Interferon-A-2B, Prevention, Hematopietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Interferon-alpha


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: standard-risk AML in CR1/CR2 without t(9;22) and t(15;17) receive HLA-identical transplantation with positive MRD before transplantation (measured by flow cytometry) CR within the first two months posttransplantation and MRD is negative between 18-60 years Exclusion Criteria: uncontrolled GVHD be in myelosuppression (WBC<1.5x10^9/L, ANC<0.5×10^9/L，PLT<25×10^9/L,HB<65g/L) severe infection organ failure the patients do not agree to participate in the study

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interferon alpha group<br>The patients in arm will be receive interferon alpha injection (3 million U/time)twice a week, as the intervention since the third month after HLA-identical transplantation. | Drug: Interferon-alpha<br>* patients in Interferon-alpha group will receive Interferon-alpha injection since the third month after transplantation for six months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cumulative incidence of relapse | the cumulative incidence of relapse | within the first year after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | overall survival | within the first year after transplantation | 
| NRM | non-relapse motality | within the first year after transplantation | 
| DFS | disease-free survival | within the first year after transplantation | 
| MRD | cumulative incidence of MRD+ | within the first year after transplantation | 
| acute GVHD | acute graft-versus-host disease | within 100 days after transplantation | 
| chronic GVHD | chronic graft-versus-host disease | within the first year after transplantation | 
| infection | bacteria, fungal, virus, etc. | within the first year after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interferon-alpha, Relapse, prevention, hematopietic stem cell transplantation, acute myeloid leukemia