Interferon-α Prevents Leukemia Relapse of AML Patients After Transplantation

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Relapse; Prevention; Interferon-A-2B; Hematopietic Stem Cell Transplantation
• Intervention / Treatment: Drug: Interferon-alpha

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 Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Interferon alpha group; 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; patients in Interferon-alpha group will receive Interferon-alpha injection since the third month after transplantation for six months.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic toxicity	any decrease of blood cells including white, red blood cells and platelet	within the first year after transplantation

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiaojun Huang, Dr., Peking University Institute of Hematology

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: April 14, 2017
• First Posted (Actual): April 19, 2017

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: prevention; acute myeloid leukemia; Relapse; Interferon-alpha; hematopietic stem cell transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Recurrence; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha
• Other Study ID Numbers: 2017PHB013-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No