Low-dose decitabine plus venetoclax maintenance after allogeneic stem cell transplant

Phase 1B/2A Study of Weekly Decitabine and Venetoclax Treatment as Maintenance Therapy in High-Risk Myeloid Malignancy Patients Post Allograft Stem Cell Transplant

This trial tests whether weekly low-dose decitabine followed 6–8 hours later by a venetoclax pill can help prevent relapse after allogeneic stem cell transplant in adults with AML or high‑risk MDS.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Case Comprehensive Cancer Center (other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Cleveland, Ohio and 1 other locations)
• Trial ID: NCT06129734 on ClinicalTrials.gov

What this trial studies

This phase 1/2 interventional trial gives participants standard post-transplant care plus weekly low-dose decitabine followed 6–8 hours later by an oral venetoclax dose. Participants will have bone marrow testing at the start, midpoint, and end of treatment, and will continue therapy for up to one year or until relapse or persistent dose-limiting toxicity. The strategy uses hypomethylating agent priming to sensitize residual leukemia cells to BCL2 inhibition with venetoclax, aiming for disease control with lower-intensity therapy. Safety, tolerability, and signs of relapse will be monitored with regular clinic visits and laboratory testing.

Who should consider this trial

Good fit: Adults (≥18) with AML or high‑risk MDS who have planned or received an allogeneic stem cell transplant, have marrow blasts <5% and no circulating blasts, ECOG 0–1, and adequate liver and kidney function are ideal candidates.

Not a fit: Patients with active relapse after transplant, marrow blasts ≥5% pre-transplant, poor performance status (ECOG >1), or significant organ dysfunction may not receive benefit from this maintenance regimen.

Why it matters

Potential benefit: If successful, this approach could reduce post-transplant relapse and improve survival while causing fewer or more manageable side effects than higher-intensity options.

How similar studies have performed: HMA plus venetoclax combinations have improved outcomes in transplant‑ineligible AML, but applying this combination as post‑transplant maintenance is relatively novel and prior post‑transplant maintenance trials have had mixed results.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of Acute myeloid leukemia, MDS, MDS/AML with high-risk for post-transplant relapse identified by:

  * Very high or high risk by CIBMTR Disease Risk Index (DRI) and/or adverse risk by ICC 2022 criteria and/or MDS/AML by ICC 2022 criteria.
  * Very high or high risk by CIBMTR DRI and/or by IPSS-M \> 0.510-12 and/or MDS/AML by ICC 2022 criteria.
* Bone marrow myeloblasts \<5% at pre-transplant bone marrow aspirate and biopsy with no circulating blasts.
* Participants must be planned for or have received alloSCT. Any conditioning regimen intensity or graft source (MRD/MUD/Haplo/UCB) is permitted.
* Participants must be 18 years of age or older.
* Total bilirubin \< 2.0 mg/dL (with the exception of participants with known Gilbert's syndrome, who should have direct bilirubin \< 2 × ULN).
* Creatinine clearance (CrCl) \> 30 ml/min.
* ECOG 0-1 performance status.
* Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures.
* Participants may enroll prior to or after alloSCT. Participants should enroll no later than post transplant day 40, and the the following post-AlloHSCT inclusion criteria must be met in order to initiate the maintenance study treatment:

  * Successful engraftment defined by absolute neutrophil count (ANC) of ≥500/ul and platelet count of ≥50,000/uL sustained for at least three consecutive days.
  * These criteria for engraftment should be met on or before Day +50.
  * No active infection
  * No GVHD ≥ overall grade II (Grade 1 GVHD of the skin acceptable).
  * Participants must continue to meet additional inclusion criteria
  * \<5% myeloblasts in a bone marrow aspirate with spicules, that is to be obtained, if all the above inclusion criteria are satisfied.

Exclusion Criteria:

* Prior disease progression on HMA/VEN therapy, single agent venetoclax.
* Other planned post-transplant maintenance therapy, such as FLT3-ITD targeting agents, as determined by the treating physician
* Currently pregnant or breast-feeding. Females of childbearing (FOCBP) potential must have negative serum pregnancy test within 72 hours from treatment start. (NOTE: FOCBP is any biologic female, regardless of sexual or gender orientation, having undergone tubal ligation, or remaining celibate by choice, who has not undergone a documented hysterectomy or bilateral oophorectomy or has had a menses any time in the preceding 12 months (therefore not naturally post-menopausal for \> 12 months)
* Uncontrolled comorbid illness that could limit life expectancy or ability to complete study correlates. This includes, but is not limited to:

  * Active infection
  * Uncontrolled concurrent malignancy
  * Congestive heart failure of NYHA class III/IV. Participants with compensated heart failure are permitted.
  * Unstable angina pectoris
  * New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted
  * Decompensated liver cirrhosis (Child-Pugh score ≥12 or a MELD score ≥21
  * Psychiatric illness/social situations that would limit compliance with study requirements.
  * Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the participants or impair the assessment of study results.
* FOCBP and males that are unwilling to agree to use dual contraceptive measures (i.e., hormonal or barrier method of birth control; abstinence, condom) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, they should inform the treating physician immediately
* Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of decitabine/venetoclax.
* Participants with known active HIV infection, as this will further increase the risk for opportunistic infections. However, participants with chronic HIV with undetectable viral load by PCR, without opportunistic infection, and on a stable regimen of antiretroviral therapy would be eligible.
* Known allergy or hypersensitivity to any component of decitabine/venetoclax

Where this trial is running

Cleveland, Ohio and 1 other locations

• Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center — Cleveland, Ohio, United States (RECRUITING)
• University Hospitals Seidman Cancer, Case Comprehensive Cancer Center — Cleveland, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: Benjamin Tomlinson, MD — University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
• Study coordinator: Benjamin Tomlinson, MD

Conditions: Myeloid Malignancy, Acute Myeloid Leukemia, Allograft Stem Cell Transplant