Overview

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

Status:
Not yet recruiting
Trial end date:
2025-12-31
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Benjamin Tomlinson
Treatments:
Decitabine
Venetoclax
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).

- Total bilirubin < 2.0 mg/dL (with the exception of participants with known
Gilbert's syndrome, who should have direct bilirubin < 2 × ULN)

- CrCl > 30 ml/min.

- ECOG 0-1 performance status.

- Participants must continue to meet all exclusion 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