Clinical trial NCT03121079: Interferon-α Prevents Leukemia Relapse of AML Patients After Transplantation
Official title: Interferon-α Prevents Leukemia Relapse of AML Patients Undergoing HLA-identical Allogeneic Hematopoietic Stem Cell Transplantation With Pretransplant MRD
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Interferon-A-2B
Relapse
Prevention
Hematopietic Stem Cell Transplantation
Keywords: Interferon-alpha
Relapse
prevention
hematopietic stem cell transplantation
acute myeloid leukemia
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2017-04-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: cumulative incidence of relapse
timeFrame: within the first year after transplantation
Secondary outcomes:
measure: OS
timeFrame: within the first year after transplantation
measure: NRM
timeFrame: within the first year after transplantation
measure: DFS
timeFrame: within the first year after transplantation
measure: MRD
timeFrame: within the first year after transplantation
measure: acute GVHD
timeFrame: within 100 days after transplantation
measure: chronic GVHD
timeFrame: within the first year after transplantation
measure: infection
timeFrame: within the first year after transplantation
Other outcomes:
measure: Hematologic toxicity
timeFrame: within the first year after transplantation
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
Study officials:
affiliation: Peking University Institute of Hematology
name: Xiaojun Huang, Dr.
role: PRINCIPAL_INVESTIGATOR
References: