RECRUITING

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

Conditions

Myeloid Malignancy Acute Myeloid Leukemia Allograft Stem Cell Transplant

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-07-28

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06129734

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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

Inclusion Criteria

Exclusion 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.

* 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

Contacts and Locations

Study Contact

Benjamin Tomlinson, MD

CONTACT

(216) 844-0139

Benjamin.tomlinson@uhhospitals.org

Principal Investigator

Benjamin Tomlinson, MD

PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

James Ignatz-Hoover, MD, PhD

PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Claudio Brunstein, MD, PhD

PRINCIPAL_INVESTIGATOR

Cleveland Clinic Foundation, Case Comprehensive Cancer Center

Study Locations (Sites)

University Hospitals Seidman Cancer, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106

United States

Collaborators and Investigators

Sponsor: Benjamin Tomlinson

Benjamin Tomlinson, MD, PRINCIPAL_INVESTIGATOR, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
James Ignatz-Hoover, MD, PhD, PRINCIPAL_INVESTIGATOR, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Claudio Brunstein, MD, PhD, PRINCIPAL_INVESTIGATOR, Cleveland Clinic Foundation, Case Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-28

Study Completion Date2027-12

Study Record Updates

Study Start Date2025-07-28

Study Completion Date2027-12

Terms related to this study

Keywords Provided by Researchers

Allograft Stem Cell Transplant

Additional Relevant MeSH Terms

Myeloid Malignancy
Acute Myeloid Leukemia