Clinical trial NCT04809181: Azacitidine in Combination With Venetoclax Treatment for MRD Positive Post Allo-HSCT AML/MDS Patients
Official title: Azacitidine in Combination With Venetoclax Treatment for Prevention of Relapse in MRD Positive Post Allogeneic Hematopoietic Stem Cell Transplantation Acute Myelogenous Leukemia/ Myelodysplastic Syndrome Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hematologic Malignancy
Stem Cell Transplant Complications
Keywords: Allogeneic Hematopoietic stem cell transplantation
Micro residual disease
Azacitidine
Venetoclax
Relapse
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Zhejiang Provincial People's Hospital
name: The First Affiliated Hospital of Zhejiang Chinese Medical University
name: Sir Run Run Shaw Hospital
name: First Affiliated Hospital of Wenzhou Medical University
name: Ningbo No. 1 Hospital
name: Yinzhou Hospital Affiliated to Medical School of Ningbo University
name: Jinhua Central Hospital
name: Taizhou Hospital
name: Union hospital of Fujian Medical University
name: Xiangya Hospital of Central South University
First posted: 2021-03-22
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: In patients with MRD-positive patients after AML/MDS allogeneic hematopoietic stem cell transplantation, azacytidine combined with venetoclax may be effective in eliminating micro residual diseases, reducing the risk of relapse, and ultimately improving long-term survival.The primary purpose of this study was to explore an effective protocol to reduce the risk of relapse in patients with MRD positive after allogeneic hematopoietic stem cell transplantation for AML/MDS.

Detailed description: The technology of Allogeneic Hematopoietic stem cell transplantation (allo-HSCT) has been continuously improved, relpase is still the leading cause of death after allo-HSCT. Monitoring of micro residual disease (MRD) after allogeneic HSCT provides a risk stratification of relpase risk in patients after transplantation.There is an urgent need to find an effective intervention plan for patients with MRD positive after transplantation, in order to reduce the risk of relapse after transplantation and improve long-term survival.The combination of demethylated drugs with venetoclax has shown promising results in clinical trials in AML patients who cannot tolerate induction chemotherapy.In patients with MRD-positive patients after AML/MDS allo-HSCT, azacytidine combined with venetoclax may be effective in eliminating small residual diseases, reducing the risk of relapse, and ultimately improving long-term survival.The primary purpose of this study was to explore an effective protocol to reduce the risk of relapse in patients with MRD positive after allo-HSCT for AML/MDS.

Eligibility criteria: Inclusion Criteria:

1. Patients between 18 years old and 65 years old.
2. Patients with AML or MDS diagnosed according to WHO diagnostic criteria.
3. Patients who received allogeneic hematopoietic stem cell transplantation and achieved complete remission.
4. MRD was positive after transplantation, MFC \> 0.1% and / or fusion gene and gene mutation (WT1 \> 0.6%, AML1-ETO \> 0.4%, others \>1%).
5. ECOG body status score 0-2.
6. Patients with expected survival time \>=3 months.
7. Good organ function level: ANC (neutrophil absolute value \>=1.0x10\^9/L; PLT \>=30x10\^9/L; HB \>=80g/L; Tibil \<=1.5 ULN; ALT / AST \<=2.5 ULN; bun / Cr \<=1.5 ULN; LVEF \>=50%).
8. Patients who have received any anti-tumor treatment (including radiotherapy, chemotherapy, surgery or molecular targeted treatment) for more than 4 weeks from the end of the previous treatment.
9. Patients with no GVHD and no previous history of 3 or more degrees of aGVHD. 10. Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing.

Exclusion Criteria:

1. Patients with severe cardiac insufficiency and EF lower than 60%; or patients with severe arrhythmia who could not tolerate super pretreatment.
2. Patients with activity of aGVHD or extensive cGVHD.
3. Patients with BCR/ABL positive.
4. Patients who were previously known to be resistant to azacytidine or dessicabine or venetoclax.
5. In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate the super pretreatment scheme.
6. Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of super pretreatment.
7. In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate the super pretreatment scheme.
8. In patients with severe active infection, the researchers evaluated that they could not tolerate the pretreatment.
9. Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.
10. Patients with hematological recurrence (bone marrow smear: proportion of primordial cells \>=5%) or any extramedullary recurrence.
11. Other reasons why the researchers could not be selected.

Primary outcomes:
measure: relapse-free survival
timeFrame: 2 year
Secondary outcomes:
measure: overall survival
timeFrame: 2 year
measure: graft-versus-host disease -free relapse-free survival
timeFrame: 2 year
measure: cumulative incidence of aGVHD
timeFrame: 100 days
measure: cumulative incidence of cGVHD
timeFrame: 2 year
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: First Affilaated Hospital of Medical School of Zhejiang University
name: Yi Luo, M.D.
role: PRINCIPAL_INVESTIGATOR
References: