Clinical trial NCT05841771: Hypomethylating Agent and Venetoclax After Allo-HSCT in Patients With High-risk Myeloid Malignancies.
Official title: A Single Arm, Phase 2 Study Evaluating Safety and Efficacy of Maintenance Therapy With Hypomethylating Agent and Venetoclax After Allogeneic Stem Cell Transplantation in Patients With f High-risk Myeloid Malignancies.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypomethylating Agent
Venetoclax
Myeloid Malignancy
Lead sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2023-05-03
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective of the study is to evaluate the efficacy and safety of maintenance therapy with hypomethylating agent and Venetoclax to improve leukemia free survival for high-risk myeloid malignancies after allogeneic hematopoietic stem cell transplantation .

Detailed description: This is a prospective single-arm study. Patients with high-risk AML or MDS aged between 18-70 years old will enroll in the study. They will be given hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days after allogeneic hematopoietic stem cell transplantation. The maintenance therapy will start from 60th days posttransplant, repeated every 28 days until up to 1-year posttransplant. The 1-year leukemia-free survival rate，1-year cumulative recurrence rate, and 1-year overall survival will be analyzed.

Eligibility criteria: Inclusion Criteria:

* Patients with AML or MDS and have received allogeneic hematopoietic cell transplantation;
* Patients with AML must have one of the following high-risk factors: Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML； require more than 2 courses of induction chemotherapy to reach complete remission； Extramedullary myeloid malignancy；≥CR2； Presence of measurable residual disease at the time of HSCT. \*
* Patients with MDS must have one of the following high-risk factors: IPSS-R scores are high-risk or very high-risk； Presence of TP53 mutation； Presence of measurable residual disease at the time of HSCT. \*
* CBC: ANC ≥ 1.0 × 10e9/L, Hb ≥ 80g/L, and PLT ≥ 50 × 10e9/L；
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

  * Presence of measurable residual disease at the time of HSCT is defined as the following: Blast percentage in bone marrow detected by flow cytometry ≥0.01%； Presence of fusion gene or mutated gene by qPCR.

Exclusion Criteria:

* Concurrent use of targeted drugs ;
* Resistant to Venetoclax before transplantation;
* Allergic to decitabine , Azacitidine or venetoclax;
* Active grade II or higher acute GVHD ;
* Active moderate or severe chronic GVHD ;
* Diseases recurrence (abnormal myeloid cells detected by flow cytometry \>0.01%, presence of WT1 or other genes, or extramedullary malignancy ), percentage of donor cells in bone marrow \<90% or graft rejection:
* CBC: ANC \< 1.0 × 10e9/L, or PLT \< 50 × 10e9/L；
* Severe organ dysfunction: Elevated Aspartate transaminase (AST) /alanine transaminase (ALT), or direct bilirubin \>3 times upper limit of normal; Creatinine clearance (Ccr)\<50mL/min or serum creatinine \>1.5 times upper limit of normal, whether hemodialysis treatment is performed;
* Active uncontrolled systemic fungal, bacterial, or viral infection
* Pregnant or lactating women;
* Other severe complications and not suitable judged by researchers.

Primary outcomes:
measure: Leukemia-free survival (LFS) time
timeFrame: From the date of transplantation, assessed up to 1 year after transplantation.
Secondary outcomes:
measure: Cumulative incidence of relapse
timeFrame: From the date of transplantation, assessed up to 1 year after transplantation.
measure: Overall survival
timeFrame: From the date of transplantation, assessed up to 1 year after transplantation.
measure: Incidence of toxicity of the regimen
timeFrame: From the date of transplantation, assessed up to 1 year after transplantation.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine Affilated Shanghai General Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine Affiliated Shanghai General Hospital
name: Liping Wan, M.D.
role: PRINCIPAL_INVESTIGATOR
References: