This study is evaluating a new treatment approach for adults with acute myeloid leukemia (AML) that has either returned after previous treatment or has not responded to treatment. Outcomes for these patients are often poor, and there is a need for more effective therapies.
The study is investigating whether adding hydroxyurea to a combination of established AML medicines (fludarabine, cytarabine, idarubicin, and venetoclax) is safe and tolerable and can improve treatment results. Laboratory studies suggest that hydroxyurea may help leukemia cells become more sensitive to treatment and may increase the effectiveness of chemotherapy.
The study is being conducted in two parts. In the first part, researchers will determine the safest and most appropriate dose of hydroxyurea when given together with the study treatment. In the second part, researchers will evaluate whether adding hydroxyurea improves treatment outcomes, including the length of time patients remain free from disease progression, relapse, or death.
The overall goal of the study is to determine whether adding hydroxyurea to standard treatment for relapsed or refractory AML is safe and may improve patient outcomes.
Refractory AML defined as having > 10% bone marrow blasts after induction with one cycle of intensive chemotherapy or no CR after two cycles of chemotherapy.
Relapsed disease (including extramedullary disease) according to the 2022 ELN criteria (see appendix A).
MRD relapse defined as evidence of measurable (minimal) residual disease (MRD) at a level of ≥5%, as determined by either molecular assays or multiparameter flow cytometry.
Age 18 years or older.
Acute promyelocytic leukemia.
WBC ≥30; pretreatment with HU to reduce the level of WBC <30 is allowed in part B/phase II of the trial.
TP53 double hit mutation / biallelic TP53 inactivation.
CNS leukemia.
Single group
Hydroxycarbamid
DrugHydroxyurea 500-1000 mg administered 1 hour before each infusion of cytarabine.
1-year EFS
Defined as event-free-survial from the time from initiation of study treatment to the first occurrence of treatment failure, hematologic relapse from CR/CRi, or death from any cause.
Safety and tolerability: incidence and severity of treatment-emergent adverse events
Frequency, nature and severity of non-hematological toxicities, including potential ara-C or fludarabine related neurological or dermatological adverse events.
Overall survival (OS)
Overall survival (OS), defined as the time from initiation of study treatment to death from any cause, with survival estimates reported at 1 and 2 years after initiation of study treatment.
2-year event-free survival (EFS)
Time from initiation of study treatment to the first occurrence of treatment failure, hematologic relapse after CR/CRi, or death from any cause, whichever occurs first.
Relapse-free survival (RFS)
Overall survival (OS), defined as the time from initiation of study treatment to the date of death from any cause or hematologic relapse from CR/CRi, with survival estimates reported at 1 and 2 years after initiation of study treatment.
Intracellular accumulation of ara-CTP and F-ara-ATP
Assessment of intracellular accumulation of ara-CTP and F-ara-ATP in circulating blasts as a biomarker for efficacy of added hydroxyurea.
SAMHD1 protein expression
Assessment of SAMHD1 protein expression in blasts before treatment as a biomarker for efficacy of added hydroxyurea
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Christer C Nilsson
Lead sponsor
Region Stockholm
Sponsor institution
Karolinska University Hospital
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
