The purpose of this study is to see the effects of an investigational combination treatment of venetoclax, azacitidine, and donor lymphocyte infusion (DLI) in patients with high-risk AML receiving allogeneic hematopoietic cell transplantation, and to assess if the combination treatment is well tolerated and prevents disease relapse after transplant.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Venetoclax will be given orally (PO) at the assigned doses of 50 or 100 mg once daily for 7, 14 or 21 days starting at day 1 of each 28-day cycle, for up to 12 cycles.
Azacitidine will be administered at a dose of 20mg/m\^2 once daily subcutaneously (SC) or intravenously (IV) for five days (Days 1-5) of each 28-day cycle.
Donor lymphocyte infusions (DLI) may be administered at the discretion of the treating physician, if certain criteria are met. Participants may receive up to three (3) infusions of donor lymphocytes (a type of white blood cell) at the following dose levels and study timepoints: * DLI 1: 1x10\^6 cluster of differentiation 3+ (CD3+) cells/kg, after cycle 3 * DLI 2: 5x10\^6 CD3+ cells/kg, after cycle 5, if there is persistent MRD * DLI 3: 1x10\^7 CD3+ cells/kg, after cycle 7, if there is persistent MRD.
University of Miami
Miami, Florida, United States
Recommended Phase 2 Dose (RP2D)
The RP2D of VEN/AZA therapy will be determined as the maximum tolerated dose of study treatment as assessed by treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 13 months
Number of Participants Experiencing Treatment-Related Toxicity
The number of participants experiencing treatment-related toxicity. Toxicity is defined as including dose limiting toxicities (DLTs), serious adverse events (SAEs) and adverse events (AEs) in study participants after starting study therapy. Toxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Time frame: Up to 13 months
Recurrence-Free Survival (RFS)
Recurrence-free survival (RFS) is defined as the elapsed time measured in months between the treatment start date (Cycle 1 Day 1) and date of documented disease recurrence or death from any cause. Alive patients without recurrence will be censored at the date of last documentation of recurrence-free status.
Time frame: Up to 24 months
Overall Survival (OS)
Overall survival (OS) is defined as the elapsed time measured in months between the treatment start date (Cycle 1 Day 1) and date of death from any cause. Alive patients will be censored at the date last known to be alive.
Time frame: Up to 24 months
Proportion of Participants with Treatment-Related Mortality (TRM)
Treatment-related Mortality (TRM) is defined as the proportion of participants that died after starting study therapy, during the time of observation and in the absence of disease progression.
Time frame: 180 days
Number of Participants with acute GVHD After Allogeneic Hematopoietic Cell Transplant (HCT)
The number of participants with acute graft-versus-host disease (aGVHD) among study participants will be reported at +100 and +180 days post-allogeneic HCT.
Time frame: Up to 180 days
Number of Participants with chronic GVHD After Allogeneic Hematopoietic Cell Transplant (HCT)
The number of participants with chronic graft-versus-host disease (cGVHD) among study participants will be reported at one (1) year post-allogeneic HCT.
Time frame: 1 year
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