This phase I trial tests the safety, side effects, best dose and how well arsenic trioxide works to prevent relapse in patients undergoing allogenic stem cell transplantation for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Chemotherapy drugs, such as arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving arsenic trioxide may be safe, tolerable and/or effective in preventing relapse in patients undergoing allogenic stem cell transplant for AML or MDS.
AML or MDS patients eligible to receive first allogeneic HCT. Eligibility inclusion for HCT is defined as per University of Michigan bone marrow transplant (BMT) standard of care criteria
TP53 loss by karyotype (chromosome 17 or 17p deletion) or single nucleotide polymorphism (SNP) (Cancer Microarray) AND ≥ one clonal TP53 mutation by next generation sequencing (NGS) (VAF > 10%).
≥ one TP53 mutation by NGS testing (with VAF > 40%)
≥ two distinct TP53 mutation(s) by NGS (VAF >10%)
Uncontrolled infections. Patients still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic, clinical and/or culture) that the infection is well controlled
Patients may NOT have evidence or symptoms of central nervous system (CNS) disease at the time of enrollment
HIV or human t-lymphotropic virus (HTLV) 1 / HTLV 2 (seropositivity and/or polymerase chain reaction [PCR] positivity)
Pregnant and nursing mothers are excluded
Single group
Allogeneic Hematopoietic Stem Cell Transplantation
Procedure/SurgeryGiven IV
Arsenic Trioxide
DrugGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Busulfan
DrugGiven IV
Fludarabine
DrugGiven fludarabine
Incidence of dose limiting toxicities
Assessed via the incidence and severity of adverse events as graded by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Progression free survival (PFS)
Malignancy relapse is defined as: evidence of persistent morphological or cytogenetic findings of acute leukemia or myelodysplastic syndrome consistent with pretransplant features occurring after primary neutrophil engraftment or day 35, whichever occurs sooner. Progression-free survival (PFS) is defined as the duration of time from HCT (Day 0) to time of death or progression of primary malignancy detected by bone marrow assessment or other clinical monitoring. Will be estimated using Kaplan-Meier methods, with specific focus on estimates and 95% confidence intervals for PFS at 6- and 12-months. If no loss to follow-up is observed, then PFS will be estimated using observed proportions.
Absolute neutrophil recovery
Engraftment for neutrophils is defined as the first of three consecutive days in which the absolute neutrophil count is \> 500/uL.
Incidence of severe cardiac arrythmia
Defined as grade 3 or greater cardiac arrythmia by CTCAE v 5.0.
Incidence of hepatic sinusoidal obstruction syndrome/veno-occlusive disease
Any Grade 3 or greater SOS/VOD by CTCAE v5.0 by day 35 post HCT will be considered for meeting this endpoint.
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