Phase 12 Study of Hydroxyurea Plus Valproic Acid or 6-Mercaptopurine Plus Valproic Acid in Adults With AML or High-Risk MDS Unfit for Standard Therapy

What this Trial Is About

Researchers are evaluating the safety, tolerability, and early effectiveness of two combination treatments for adults aged 18 and older with acute myeloid leukemia AML or high-risk myelodysplastic syndrome HR-MDS who are unfit or ineligible for standard therapies. The study focuses on patients newly diagnosed, relapsed, or refractory to treatments and aims to explore combinations of well-known drugs with low toxicity, hoping to improve overall survival and quality of life in this vulnerable population. This open-label phase 12 study includes sites in Norway and other Nordic countries and uses an adaptive design to assess clinical benefit efficiently. The study has two treatment combinations combination 1 uses hydroxyurea and valproic acid, while combination 2 uses 6-mercaptopurine and valproic acid. Each participant begins with combination 1 for a 28-day cycle involving 14 days of medication followed by 14 days off. If no clinical benefit or unacceptable toxicity occurs after the first cycle, the participant switches to combination 2 with a similar 28-day cycle. Treatment continues for up to six cycles as long as clinical benefit is observed. The study includes a cohort expansion phase if initial results are promising, with detailed dosing and switching rules to avoid prolonged ineffective treatments. Participants will have regular visits every week during the first cycle and every 28 days thereafter for assessments including safety, tolerability, clinical benefit, performance status, quality of life, and survival. Laboratory tests and tumor debulking are done before each cycle to manage white blood cell levels. Researchers will monitor outcomes such as treatment response, duration of benefit, disease progression, hospitalization, and transfusion rates over a treatment period of up to six months, followed by six months of follow-up. The total study duration is about five years, allowing comprehensive evaluation of these treatment combinations.

A Study to Investigate Treatment of HU and VPA, or 6-MP and VPA in Unfit AML/HR-MDS Patients