Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN.
Hartmut Döhner, Andrew H Wei, Frederick R Appelbaum...
https://pubmed.ncbi.nlm.nih.gov/35797463Actively Recruiting
Phase 1
Phase 2
Age: 18Years +
All Genders
ID06199557
A Phase 1/2 Study of Hydroxyurea Plus Valproic Acid or 6-Mercaptopurine Plus Valproic Acid in Adults With AML or HR-MDS Unfit for Standard Therapy
Led by Haukeland University Hospital · Updated on 2025-06-29
48
Participants Needed
1
Research Sites
200 weeks
Total Duration
On this page
AI-Summary
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 1/2 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.
CONDITIONS
Brief Title
A Study to Investigate Treatment of HU and VPA, or 6-MP and VPA in Unfit AML/HR-MDS Patients
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Male or female aged 18 years or older
- Written informed consent provided
- Newly diagnosed AML as defined by ELN 2022 criteria, or relapsed/refractory AML unfit for standard therapy or who declined it
- Newly diagnosed or relapsed/refractory high-risk myelodysplastic syndrome unfit for standard therapy or who declined it
- Secondary AML (MDS-related or therapy-induced), or acute promyelocytic leukemia not eligible for standard therapy
- Adequate kidney function (serum creatinine ≤1.5 x ULN, creatinine clearance ≥40 mL/min)
- Adequate liver function (bilirubin ≤1.5 x ULN; AST and ALT ≤2.5 x ULN or ≤5 x ULN with liver metastases; ALP ≤2.5 x ULN)
- ECOG performance status 0 to 3
- Female patients of childbearing potential must have a negative pregnancy test within 3 days before starting treatment
- Agree to use effective contraception during the study and for more than 3 months after last dose
- Female patients not of childbearing potential defined by surgical sterility or post-menopausal status
You will not qualify if you...
- Receiving anti-leukemic therapy or investigational agents within 2 weeks before enrollment
- Active malignancy within past 6 months except certain skin or cervical cancers
- Severe or uncontrolled medical conditions at investigator's discretion
- Breastfeeding women
- Cardiac dysfunction including recent myocardial infarction, severe heart failure, unstable angina, or arrhythmias
- COVID-19 infection or vaccine within 7 days before study start
- History of poor compliance with medical regimens
- Serious medical conditions that could compromise study participation
- Dementia, mental impairment, or psychiatric disorders preventing informed consent
- Current chemotherapy, radiation, or immunotherapy other than specified in protocol
- Known allergy to study medications or their ingredients
- Conditions that may affect compliance with study procedures and follow-up
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 6 cycles of 28 days each
Participants receive treatment cycles with hydroxyurea plus valproic acid for the first cycle. If they do not experience clinical benefit or have unacceptable toxicity, they switch to 6-mercaptopurine plus valproic acid. Each treatment cycle includes 14 days of medication followed by 14 days without medication.
Weekly visits during the first cycle, then visits every 28 days for subsequent cycles
Trial Site Locations
Total: 1 location
1
Haukeland University Hospital
Bergen, Bergen, Norway, 5021
Actively Recruiting
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Research Team
B
Bjørn Tore Gjertsen, MD, PhD
I
Irini Ktoridou-Valen, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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Published Research Related To This Trial
Acute myeloid leukemia.
B Löwenberg, J R Downing, A Burnett
https://pubmed.ncbi.nlm.nih.gov/10502596Hydroxyurea-The Good, the Bad and the Ugly.
Marcelina W Musiałek, Dorota Rybaczek
https://pubmed.ncbi.nlm.nih.gov/34356112Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents.
Hanne Fredly, Bjørn Tore Gjertsen, Oystein Bruserud
https://pubmed.ncbi.nlm.nih.gov/23898968Hydroxyurea synergizes with valproic acid in wild-type p53 acute myeloid leukaemia.
Calum Leitch, Tereza Osdal, Vibeke Andresen...
https://pubmed.ncbi.nlm.nih.gov/26812881Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.
Pierre Fenaux, Ghulam J Mufti, Eva Hellstrom-Lindberg...
https://pubmed.ncbi.nlm.nih.gov/19230772Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome.
Andres O Soriano, Hui Yang, Stefan Faderl...
https://pubmed.ncbi.nlm.nih.gov/17596541Molecular and therapeutic potential and toxicity of valproic acid.
Sébastien Chateauvieux, Franck Morceau, Mario Dicato...
https://pubmed.ncbi.nlm.nih.gov/20798865Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients.
Michela Tassara, Konstanze Döhner, Peter Brossart...
https://pubmed.ncbi.nlm.nih.gov/24797300Historical background of 6-mercaptopurine.
G B Elion
https://pubmed.ncbi.nlm.nih.gov/3538499