Interferon-α Prevents Leukemia Relapse of AML Patients After Transplantation

Not Applicable

Withdrawn

• Conditions: Prevention; Hematopietic Stem Cell Transplantation; Interferon-A-2B; Relapse
• Interventions: Drug: Interferon-alpha

• Registration Number: NCT03121079
• Lead Sponsor: Peking University People's Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-04-14
• Study First Submitted QC: 2017-04-14
• Study First Posted: 2017-04-19
• Study Start: 2017-05-01
• Primary Completion: 2019-12-31
• Study Completion: 2019-12-31
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-21
• Last Update Posted: 2020-09-23

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Interferon alpha group	Interferon-alpha	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.

Primary Outcome Measures

Name	Time	Method
cumulative incidence of relapse	within the first year after transplantation	the cumulative incidence of relapse

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Beijing, China