IRB Study Number 25-532
Status Recruiting
Institute Taussig Cancer Institute
Description
2.1 Primary Objectives
The primary objective in the Phase 1B/2A trial is to assess the safety and feasibility of posttransplant maintenance with the once a week decitabine + venetoclax treatment regimen.
2.2 Secondary Objective(s)
The secondary objective of this Phase 1B/2A trial is to assess one year post transplant relapse free survival in transplant patients treated with decitabine/venetoclax.
2.3 Correlative/Exploratory Objective(s)
The exploratory objectives of this trial will provide proof of concenpt that decitabine/venetoclax is depleting DMNT1 levels, stimulating the AML ISR, and promoting increased sensitivity to BCL2 inhibition.
We will also assess the effects of our treatment on measurable residual disease (MRD) assessments. MRD is monitored per institutional standards utilizing flow cytometry based and qPCR based platforms.
Inclusion Criteria
- Diagnosis of Acute myeloid leukemia, MDS, MDS/AML with high-risk for posttransplant relapse identified by:
a. Very high or high risk by CIBMTR Disease Risk Index (DRI) and/or adverse risk by ICC 2022 criteria10,11 and/or MDS/AML by ICC 2022 criteria10,11.
b. MDS: Very high or high risk by CIBMTR DRI and/or by IPSS-M > 0.510,11,13 and/or MDS/AML by ICC 2022 criteria10,11.
Bone marrow myeloblasts <5% at pre-transplant bone marrow aspirate and biopsy with no circulating blasts.
Patients must be planned for or have received allo SCT. Any conditioning regimen intensity or graft source (MRD/MUD/Haplo/UCB) is permitted
Patients must be 18 years of age or older
Total bilirubin < 2.0 mg/dL (with the exception of patients 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.
Patients may enroll prior to or after allo SCT. Patients should enroll no later than post transplant day 40, and the the following post-Allo HSCT inclusion criteria must be met in order to initiate the maintenance study treatment:
a. 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
b. These criteria for engraftment should be met on or before Day +50.
c. No active infection
d. No GVHD ≥ overall grade II (Grade 1 GVHD of the skin acceptable).
e. Patients must continue to meet additional inclusion criteria
f. <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 postmenopausal for > 12 months)
Uncontrolled comorbid illness that could limit life expectancy or ability to complete study correlates. This includes, but is not limited to:
a. Active infection
b. Uncontrolled concurrent malignancy
c. Congestive heart failure of NYHA class III/IV. Patients with compensated heart failure are permitted.
d. Unstable angina pectoris
e. New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted
f. Decompensated liver cirrhosis (Child-Pugh score ≥12 or a MELD score ≥21
g. Psychiatric illness/social situations that would limit compliance with study requirements.
h. Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the patient 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.
Patients with known active HIV infection, as this will further increase the risk for opportunistic infections. However, patients 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
