Combining azacitidine and venetoclax for patients with MRD-positive AML/MDS after stem cell transplant

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

This study is testing if a combination of azacitidine and venetoclax can help adults with acute myeloid leukemia or myelodysplastic syndromes who still have small traces of cancer after a stem cell transplant to stay in remission longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 95 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT04809181 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of azacitidine in combination with venetoclax for patients who are MRD-positive following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The study aims to reduce the risk of relapse by targeting micro residual disease, which is a significant concern after transplantation. Eligible participants include adults aged 18 to 65 who have achieved complete remission but still show signs of MRD. The trial will monitor the impact of this treatment combination on long-term survival and relapse rates.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 who have undergone allogeneic stem cell transplantation for AML or MDS and are MRD-positive.

Not a fit: Patients who have severe graft-versus-host disease (GVHD) or those with a poor prognosis due to other health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of relapse and improve long-term survival for patients with MRD-positive AML/MDS.

How similar studies have performed: Other studies have shown promising results with similar combinations of demethylating agents and venetoclax in treating AML, indicating potential for success in this approach.

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.

Where this trial is running

Hangzhou, Zhejiang

• The first Affiliated Hospital of Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Yi Luo, M.D. — First Affilaated Hospital of Medical School of Zhejiang University
• Study coordinator: Yi Luo, M.D.

Conditions Hematologic Malignancy; Stem Cell Transplant Complications; Allogeneic Hematopoietic stem cell transplantation; Micro residual disease; Azacitidine; Venetoclax; Relapse