Using hypomethylating agents and Venetoclax for leukemia treatment after stem cell transplant

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.

This study is testing if a combination of two medications can help people with high-risk leukemia stay cancer-free after a stem cell transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05841771 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of maintenance therapy with hypomethylating agents and Venetoclax in patients with high-risk myeloid malignancies following allogeneic hematopoietic stem cell transplantation. It is a prospective single-arm study involving patients aged 18-70 years with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Participants will receive hypomethylating agents for 5 days and Venetoclax for 7 days starting from 60 days post-transplant, with treatment cycles repeated every 28 days for up to one year. The study aims to analyze the one-year leukemia-free survival rate, cumulative recurrence rate, and overall survival.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-70 with high-risk AML or MDS who have undergone allogeneic hematopoietic stem cell transplantation.

Not a fit: Patients with low-risk myeloid malignancies or those who have not received a stem cell transplant may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve leukemia-free survival rates for patients with high-risk myeloid malignancies after transplantation.

How similar studies have performed: Other studies have shown promising results with similar approaches, indicating potential for success in this novel application.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Jiao Tong University School of Medicine Affilated Shanghai General Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Liping Wan, M.D. — Shanghai Jiao Tong University School of Medicine Affiliated Shanghai General Hospital
• Study coordinator: Xueying Ding, Ph.D.

Conditions: Hypomethylating Agent, Venetoclax, Myeloid Malignancy