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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Hydroxyurea 500-1000 mg administered 1 hour before each infusion of cytarabine.
Medical Unit Hematology, Karolinska University Hospital
Stockholm, Sweden
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.
Time frame: 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, assessed up to 365 days.
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.
Time frame: From registration in the study until 60 days after the last dose of treatment.
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.
Time frame: From initiation of study treatment through 2 years of follow-up.
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.
Time frame: From initiation of study treatment through 2 years of follow-up.
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.
Time frame: From initiation of study treatment through 2 years of follow-up.
Cumulative incidence of hematologic relapse
Cumulative incidence of hematologic relapse after achievement of CR/CRi, reported at 1 and 2 years. Death without prior relapse will be treated as a competing risk.
Time frame: From initiation of study treatment through 2 years of follow-up.
Response rate
Proportion of patients achieving complete remission (CR), complete remission with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) and minimal residual disease (MRD) negativity.
Time frame: At response assessment after Cycle 1 (between Day 25 and Day 35 from the start of Cycle 1).
Time to hematopoietic recovery
Time to hematopoietic recovery (ANC 0.5 and 1.0 x 109/L; platelets 50 and 100 x 109/L) after each chemotherapy treatment cycle, defined as the time from the start of the cycle until recovery.
Time frame: From the start of each treatment cycle until hematopoietic recovery. Treatment cycles are of variable duration, with no predefined cycle length; the subsequent cycle is initiated only after hematopoietic recovery.
Rate of patients bridged to allo-HCT
Proportion of patients undergoing allogeneic hematopoietic cell transplantation.
Time frame: From treatment initiation until allogeneic hematopoietic cell transplantation, relapse/progression, death, or 2 years of follow-up, whichever occurs first.
Early mortality (30-day and 60-day mortality)
Proportion of patients who die from any cause within 30 and 60 days after initiation of study treatment.
Time frame: 30 and 60 days after initiation of study treatment.
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