NCT07737769Not yet recruitingPhase 1
A Phase I Non-Randomized Study of TP53 Reactivation With Arsenic Trioxide in Allogeneic Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome
University of Michigan Rogel Cancer Center1 site in 1 country20 target enrollmentStarted: November 1, 2026Last updated:
Conditions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Incidence of dose limiting toxicities
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 21 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Presence of high-risk AML/MDS with probable biallelic TP53 deletion or mutation status, defined by one of the following in prior blood or bone marrow assessments:
- •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%)
- •Evidence that at least one TP53 allele harbors a structural TP53 missense mutation. In cases where the mutation type is unclassified, molecular pathology assessment is required to determine if one of the lesions is a missense mutation (as described in NGS report)
- •Patients may be enrolled with either active disease or in morphological remission, provided the bone marrow blast count on the pre-HCT assessment does not exceed 30%
- •Age > 21 years at enrollment and receiving allogeneic HCT in the adult transplant program
- •Karnofsky performance score (KPS) ≥ 70%
- •Documentation of adequate pulmonary function by forced expiratory volume and 1 second (FEV1) ≥ 50% of predicted, forced vital capacity (FVC) ≥ 50% of predicted and DLCO (corrected for hemoglobin) ≥ 50% of predicted (must meet all criteria at time of enrollment based on standard of care pre HCT testing)
- •Transthoracic echocardiogram with ejection fraction ≥ 50% (must meet all criteria at time of enrollment based on standard of care pre HCT testing)
- •Estimated glomerular filtration rate ≥ 50% ml/min/1.73m^2 by the Cockcroft-Gault equation. Glomerular filtration rate (GFR) should be corrected for body surface area (BSA) (must meet all criteria at time of enrollment based on standard of care pre HCT testing)
- •Total bilirubin ≤ 2 x upper limit of normal (unless directly attributed to Gilbert's Syndrome) (must meet all criteria at time of enrollment based on standard of care pre HCT testing)
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (must meet all criteria at time of enrollment based on standard of care pre HCT testing)
- •Electrocardiogram (ECG) with corrected QT (QTc) ≤ 450 msec (using the Framingham correction) (must meet all criteria at time of enrollment based on standard of care pre HCT testing)
- •Availability of an 8 of 8 HLA matched unrelated donor with matching at HLA A, B, C and DRB1
- •Availability of a peripheral blood stem cell (PBSC) product
- •Ability to understand and the willingness to sign a written informed consent
- •Willingness to agree to use adequate contraception methods (subjects of reproductive potential only):
- •Females of reproductive potential must agree to use effective contraception (e.g., hormonal contraception, intrauterine device, tubal occlusion, vasectomized partner, abstinence) during treatment with ATO and for 6 months after the final dose.
- •Males with female partners of reproductive potential must agree to use effective contraception during treatment with ATO and for 3 months after the final dose
Exclusion Criteria
- •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
- •Any physical, psychological or psychosocial condition that, in the opinion of the investigator, would pose unacceptable risk to the patient
- •Other malignancy requiring systemic therapy or with life expectancy of < 1 year
- •Receipt of prior allogeneic HCT
- •History of severe cardiac conduction abnormalities (complete heart block, Left Bundle Branch Block, Torsades de Pointes, or other ventricular arrythmias). History of any cardiac arrhythmia (e.g. rate controlled atrial fibrillation) is not an exclusion
- •QTc > 450 msec (using the Framingham correction)
- •Patients under 40 years of age at time of evaluation will be screened for Shwachman-Diamond syndrome (SDS), which is a rare, inherited disorder characterized primarily by exocrine pancreatic insufficiency, bone marrow failure, and skeletal abnormalities. These patients commonly progress to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Given potential for increased liver toxicities in this population, these patients will be excluded from the study. All patients under 40 years old will be screened through the University of Michigan Prevention Genetics Clinic prior to enrollment
- •Patients with known hypersensitivity to arsenic
Outcomes
Primary Outcomes
Incidence of dose limiting toxicities
Time Frame: From baseline to day 35 post hematopoietic stem cell transplant (HCT)
Assessed via the incidence and severity of adverse events as graded by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Secondary Outcomes
- Progression free survival (PFS)(At 6 and 12 months post HCT)
- Absolute neutrophil recovery(From day 0 to day 35 post HCT)
- Incidence of severe cardiac arrythmia(From baseline to day 35 post HCT)
- Incidence of hepatic sinusoidal obstruction syndrome/veno-occlusive disease(From baseline to day 35 post HCT)
- PFS(At 12 months post HCT)
- Incidence of non-relapse mortality (NRM)(At 6 and 12 months post HCT)
- Incidence of acute graft versus host disease(At 6 months post HCT)
- Incidence and severity of chronic graft versus host disease(At 6 and 12 months post HCT)
Investigators
Study Sites (1)
Loading locations...
Similar Trials
Recruiting
Phase 1
A trial to learn how safe AZD5335 is and if a drug called itraconazole changes how AZD5335 moves through the body over time in adults with ovarian, peritoneal, or fallopian tube cancer2025-522731-34-00AstraZeneca AB17
Not yet recruiting
Phase 1
A Phase I Clinical Study of AK150 in Advanced Malignant Solid TumorNCT07566247Akeso96
Not yet recruiting
Phase 1
A Phase I Trial of QLS2313 Injection in Relapsed/Refractory Hematological MalignanciesNCT07294300Qilu Pharmaceutical Co., Ltd.124
Completed
Phase 1
Single Ascending Dose Study(SAD),Multiple Ascending Dose Study(MAD) , High-fat Diet Study (FE) of TJ0113 Capsules in Healthy SubjectsNCT07394452Hangzhou PhecdaMed Co., Ltd.130
Not yet recruiting
Phase 2/3
To Study Effect of Triphaladi Kalk in Mutrakriccha with special reference to urinary tract infectionCTRI/2026/03/106644Dr Neha Jagannath Bhujbal80