Decitabine and Venetoclax Treatment as Maintenance Therapy in Patients Post Allograft Stem Cell Transplant

NCT06129734 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE2923
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this interventional clinical trial is to determine if low doses of gentle chemotherapy after bone marrow transplant may prevent relapse and promote an increase in survival and decrease in side effects in participants with acute myeloid leukemia and myelodysplastic syndromes. The main question it aims to answer is whether or not providing a new, gentler way of administering chemotherapy will help control leftover cancer with minimal side effects. This treatment involves decitabine and venetoclax. Participants will receive standard post-transplant care. Participants will be administered decitabine once per week with normal transplant follow up visits, and then will take a venetoclax pill about 6 to 8 hours later. Participants will meet their study team at the beginning, midway, and at the end of the trial to receive bone marrow testing. Participants will receive treatment until either one year of therapy, relapse, or recurrent dose limiting toxicity (DLT) despite dose reduction.

Conditions

Myeloid Malignancy; Acute Myeloid Leukemia

Keywords

Allograft Stem Cell Transplant

Outcome Measures

Primary Outcomes (2)

• Safety as measured by dose limiting toxicities

  The primary objective of this study will be to assess the safety of low dose decitabine/venetoclax in the post transplant setting. Safety will be defined in accordance with FDA guidance on development for new therapeutics in AML with the particular criteria to be considered as DLTs. The stopping criteria are described for the incidence of dose limiting toxicities that are at least possibly related to the study treatment. Using Bayesian toxicity monitoring with maximum DLT probability as 0.15, prior distribution (0.5, 0.5), maximum participants 20, minimum number of participants before stopping 9, cohort size 5, and posterior probability 0.8, the study will be paused for review if (2, 3, 4, 5) or more participants experiencing such Grade 4 events in (69, 11, 16, 20) participants, respectively.

  1 year after treatment

• Feasibility as measured by the rate of participants receiving planned treatment

  The primary objective of this study will be to assess the feasibility of low dose decitabine/venetoclax in the post transplant setting. Feasibility will be defined as ≥ 80% of participants receiving ≥80% of planned decitabine/venetoclax doses, excluding participants removed from the study in the event of relapse.

  1 year after treatment

Secondary Outcomes (1)

• Rate of relapse free survival

  1 year after treatment

Study Arms (1)

Low dose maintenance chemotherapy

EXPERIMENTAL

Participants will receive low dose chemotherapy as a maintenance therapy post-transplant. Participants must enroll by post-transplant day 40. Treatment will consist of once weekly 5 mg/m2 decitabine followed by 400 mg venetoclax orally approximately 6 hours afterwards. Participants will continue maintenance therapy for one year or unacceptable toxicity. Participants will otherwise receive post Allogeneic hematopoietic stem cell transplant (alloSCT) care and disease monitoring as per institutional standards.

Drug: Venetoclax; Drug: Decitabine

Interventions

Venetoclax DRUG

Venetoclax is a BCL2 inhibitor. It is administered at low doses and used in combination with other hypomethylating agents such as decitabine to manage participants with acute myeloid lymphoma who have undergone stem cell transplant. Participants will initiate therapy with decitabine that will be followed by venetoclax 400 mg oral 6-8 hours later. Participants will continue this dose each week. The venetoclax dose will be reduced to 100 mg once per week if the participant is being treated with posaconazole or voriconazole (strong CYP3A4 inhibitors) (considered dose equivalent to venetoclax 400 mg 1X/week). The venetoclax dose will be reduced 200 mg once per week if the participant is being treated with fluconazole or isavuconazole (moderate CYP3A4 inhibitors) (considered dose equivalent to venetoclax 400 mg 1X/week). This clinical trial is administering venetoclax well below the current FDA approved dosing.

Low dose maintenance chemotherapy

Decitabine DRUG

Decitabine is a hypomethylating agent. It is administered at low doses and used in combination with venetoclax to manage participants with acute myeloid lymphoma who have undergone stem cell transplant. Participants initiate therapy with 5 mg/m2 decitabine subcutaneous every week followed by venetoclax.

Low dose maintenance chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Benjamin Tomlinson: lead

Study Sites (2)

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

University Hospitals Seidman Cancer, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Benjamin Tomlinson, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• James Ignatz-Hoover, MD, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Claudio Brunstein, MD, PhD

  Cleveland Clinic Foundation, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Tomlinson, MD

CONTACT

(216) 844-0139; Benjamin.tomlinson@uhhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: November 13, 2023
• Study Start: July 28, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Compiled and analyzed patient data will be published upon study completion. Publisher may request Protocol and Statistical Analysis Plan
• Access Criteria: Investigators who provide a methodologically sound proposal for use of requested data

Locations

US (2)