Using azacitidine and venetoclax to treat acute myeloid leukemia before a stem cell transplant

A Phase 2 Study of Azacitidine and Venetoclax to Treat Acute Myeloid Leukemia Patients With Measurable Residual Disease Before an Allogeneic Stem Cell Transplant

This study is testing if the combination of azacitidine and venetoclax can help adults with acute myeloid leukemia stay cancer-free after a stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT06773208 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of azacitidine and venetoclax in reducing measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) who have undergone standard chemotherapy and are preparing for an allogeneic hematopoietic stem cell transplant. Participants must be in morphologic remission after receiving two cycles of intensive chemotherapy. The goal is to determine if this combination therapy can improve outcomes by lowering the chances of disease relapse post-transplant.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of de-novo AML who have achieved morphologic remission after intensive chemotherapy.

Not a fit: Patients who have not achieved remission or those with acute promyelocytic leukemia (APL) may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could significantly improve remission rates and reduce the risk of relapse in AML patients undergoing stem cell transplantation.

How similar studies have performed: Other studies have shown promising results with similar treatment combinations in AML, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 1\. Adult patient ≥18 years of age at the time of signing the informed consent form (ICF). Legal Authorized Representatives (LAR) are permitted.

  2\. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.

  3\. Patient has a confirmed diagnosis of de-novo AML (non-APL) as per World Health Organization (2022) guidelines. All (non-APL) subtypes of AML are permitted, irrespective of ELN risk category or mutational status.

  4\. Patient has received 1-3 cycles of intensive chemotherapy for remission induction.

  5\. Patient is in a morphologic remission, defined as less than 5% percent blasts seen by aspirate differential (or immunohistochemistry if no aspirate available) from bone marrow biopsy.

  6\. Patient and is either in CR, or CR with partial count recovery, either CRi/CRh\\\^1.

  1CR= BM with \<5% blasts, absence of circulating blasts; absence of extramedullary disease, absolute neutrophil count (ANC) ≥ 1000 cells/µL and platelet (PLT) count ≥ 100,000/µL. CRh = CR with ANC 500-1000 cells/µL and PLT 50,000-100,000 /µL. CRi = CR without meeting CRh criteria (residual neutropenia or thrombocytopenia).

  7\. Patient has positive measurable residual disease (MRD) at or above a level of 0.1%, by flow cytometry (MFC) or in molecular cases (NPM1 mutated or one of the CBF translocations) RT-qPCR at or above 0.01%, as described above (see section 3.6). If RT-qPCR is not available, MFC will be allowed for determining eligibility for molecular patients (at or above 0.1%).

  8\. Patient is eligible for intensive chemotherapy and immediate allogeneic transplant, with intention to proceed to transplant after trial intervention.

  9\. Patient has an ECOG performance status of ≤3 10. Patient has adequate organ function defined as:
  1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  2. Serum total bilirubin \< 1.5 x ULN (or direct bilirubin normal in subjects with total bilirubin \> 1.5 ULN). Except in cases of Gilbert's disease.
  3. Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation.

     11\. Absence of active uncontrolled infection, heart failure or severe psychiatric or neurological disease.

     12\. Females of childbearing potential may participate provided they have a negative serum pregnancy test at screening and a negative serum OR urine pregnancy test within two weeks of starting on treatment.

     13\. Females of reproductive potential should use effective contraception during the study, and for 6 months after last dose of azacitidine. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after.

     Exclusion Criteria:

     1\. Patients with acute promyelocytic leukemia (APL) or relapsed/refractory AML 2. Blast crisis of chronic myeloid leukemia 3. Patient with 5% blasts or more by bone marrow aspirate differential (or IHC if no aspirate available) 4. Patient has received previous therapy with a venetoclax containing regimen. 5. Patient has presence of any other condition that may increase the risk associated with study participation, and in the opinion of the investigator, would make the patient inappropriate for entry into the study.

     6\. Patient has active uncontrolled systemic fungal, bacterial, or viral infection.

     7\. Patient had recent, significant venous or arterial thrombotic event that would necessitate full anticoagulation or dual anti-platelet therapy, including PE within 30 days prior to start of treatment or insertion of drug eluting stent within 6 months prior to start of treatment. Chronic indications for anticoagulation such as atrial fibrillation, can be included if CHADS2 score below 4.

     8\. Patient has mechanical heart valve. 9. Patient had recent significant hemorrhagic episode, at the discretion of investigator.

     10\. Patient has significant active cardiac disease within 6 months prior to start of study treatment.

     11\. Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.

     12\. Female subject who is pregnant or lactating.

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering at Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (All Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (All Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (All Protocol Activities) — Rockville Centre, New York, United States (Recruiting)

Study contacts

• Principal investigator: Eytan Stein, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Meira Yisraeli Salman, MD

Conditions Acute Myeloid Leukemia; Azacitidine; Venetoclax; Allogeneic Stem Cell Transplant; 24-347