AzTrials
AzTrials

Acute Myeloid Leukemia, AdultPhase 1/2HUVAMERNCT06199557

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

A Phase 1/2 study testing Hydroxyurea, Hydroxycarbamide, Valproic acid and 6-Mercaptopurine (6-MP) in people with Acute Myeloid Leukemia, Adult and Myelodysplastic Syndromes, Adult, run by Haukeland University Hospital at 1 site in Norway.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to investigate the safety, tolerability, and preliminary efficacy of the combination treatment of hydroxyurea capsules and valproic acid capsules, or the combination treatment of 6-mercaptopurine tablets and valproic acid capsules in male and female patients aged 18 years or older with… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hydroxyurea, Hydroxycarbamide, Valproic acid and 6-Mercaptopurine (6-MP)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteNorway
Study dates
23 May 2024to 30 Sep 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants are eligible for the study only if all of the following criteria apply:
  • o Female or male, age 18 years or older
  • Written informed consent
  • Patients with Newly diagnosed AML, as defined by ELN 2022 criteria, or relapsed/refractory AML who: - are unfit, defined as HCT-CI ≥ 3, or - in the opinion of the investigator are not candidates for standard therapy or unlikely to tolerate or derive significant clinical benefit from standard therapy, or
  • the patient has declined standard therapy
  • Newly diagnosed HR-MDS, or relapsed/refractory HR-MDS who:
Show all 29Show fewer
  • are unfit, defined as HCT-CI ≥ 3, or
  • in the opinion of the investigator are not candidates for standard therapy or unlikely to tolerate or derive significant clinical benefit from standard therapy, or
  • has declined standard therapy
  • Secondary AML (MDS-related/ therapy- induced), or
  • Acute promyelocytic leukemia not eligible for standard therapy and/or specific therapy.
  • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
  • Serum creatinine ≤1.5 x ULN;
  • Estimated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault equation);
  • Hepatic function;
  • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); ii. Aspartate aminotransferase (AST)
  • ≤2.5 × ULN
  • ≤5 × ULN for patients with liver metastases
  • Alanine aminotransferase (ALT)
  • <!-- -->
  • ≤2.5 × ULN
  • ≤5 × ULN for patients with liver metastases
  • Alkaline phosphatase (ALP)
  • 1. ≤2.5 × ULN
  • European Cooperative Oncology Group (ECOG) performance status 0, 1, 2 or 3
  • Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to taking their first dose of study medication. Male patients and female patients of reproductive potential must agree to practice highly effective methods of contraception (such as hormonal implants, combined oral contraceptives, injectable contraceptives, intrauterine device with hormone spirals, total sexual abstinence, vasectomy) throughout the study and for >3 months after the last dose of study medication. Female patients are considered NOT of childbearing potential if they have a history of surgical sterility or evidence of post-menopausal status defined as any of the following:
  • Natural menopause with last menses >1 year ago
  • Radiation induced oophorectomy with last menses >1 year ago
  • Chemotherapy induced menopause with last menses >1 year ago

Who cannot join

  • Participants are excluded from the study if any of the following criteria apply:
  • Patients on treatment for AML (any anti-leukemic therapy including investigational agents) or treated less than 2 weeks before inclusion.
  • Concurrent history of active malignancy in the past six months prior to diagnosis except for
  • basal and squamous cell carcinoma of the skin
  • in situ carcinoma of the cervix
  • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease et cetera) at the investigators discretion.
Show all 19Show fewer
  • Breastfeeding women
  • Cardiac dysfunction as defined by:
  • myocardial infarction within the last 3 months of study entry, or
  • congestive heart failure NYHA class IV or
  • unstable angina, or
  • unstable cardiac arrhythmias
  • SARS-CoV-2 infection < 7 days or Covid-19-vaccine < 7 days from study onset
  • Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
  • Patients with any serious concomitant medical condition that could, in the opinion of the investigator, compromise participation in the study.
  • Patients with senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  • Known hypersensitivity to study medications or its excipients.
  • Any psychological, familial, sociological, and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Bjørn Tore Gjertsen, MD, PhD contact

004741566248

bjorn.tore.gjertsen@helse-bergen.no

Irini Ktoridou-Valen, MD contact

004746664928

irini.ktoridou-valen@helse-bergen.no

Norway1 site, 1 recruiting

  • Haukeland University Hospital

    Bergen, Bergen, 5021

    Bjørn Tore Gjertsen, MD, PhD, 004741566248, bjorn.tore.gjertsen@helse-bergen.no

    Irini Ktoridou-Valen, MD, 004746664928, irini.ktoridou-valen@helse-bergen.no

    Recruiting

Other trials in Norway

About this study

Official title: A Phase 1/2 Multicenter Open-label Study to Investigate Treatment of Hydroxyurea in Combination With Valproic Acid (VPA), or 6- Mercaptopurine in Combination With VPA in Patients With AML or HR-MDS Unfit for Standard Therapy

The purpose of this study is to investigate the safety, tolerability, and preliminary efficacy of the combination treatment of hydroxyurea capsules and valproic acid capsules, or the combination treatment of 6-mercaptopurine tablets and valproic acid capsules in male and female patients aged 18 years or older with acute myeloid leukemia or high- risk myelodysplastic syndrome.

The population to be studied is newly diagnosed AML patients who are considered unfit for standard induction chemotherapy, HR-MDS unfit/ineligible for standard treatment, and relapsed/refractory AML/HR-MDS patients who are considered unfit for standard therapy ,or are, for some reason, ineligible for another type of therapy. Clinically, hydroxyurea, valproic acid and 6-mercaptopurine are historically very well-known therapeutic agents with low toxicity profiles. The rationale for this study is that the combination of these drugs with low toxicity will be well tolerated in elderly AML patients with comorbidities, or lower performance status. This combination could have a beneficial therapeutic effect on overall survival and contribute to a better quality of life.

Read the detailed description

This a two-part, open-label phase 1/2 study that will include clinical sites in Norway and other Nordic countries.

The study consists of part A and part B. Part A will run in Norway only. Part B will run in Norway and the Nordic countries.

Both part A and part B have two different treatment combinations (T), combination 1 and combination 2. Part B is a cohort expansion of part A (if part A proves to be positive).

Treatment combination 1 (T1): hydroxyurea + valproic acid. Treatment combination 2 (T2): 6-mercaptopurine + valproic acid.

Each patient enrolled in the trial will start and will receive at least one cycle with T1:

hydroxyurea and valproic acid. The first cycle in the study always constitutes of hydroxyurea (1000 mg twice a day) plus valproic acid (300 mg + 600 mg) for 14 days; this will be followed by a 14-day period with no medication. Each cycle duration is 28 days.

Patients who do not experience clinical benefit after the first cycle will not be eligible to continue on this regimen and they will be allocated to treatment combination 2. On the other hand, patients who do experience clinical benefit after cycle 1 with combination 1 (HU + VPA) will be further eligible to continue on this regimen/combination. However, patients on T1 will be withdrawn after consequent cycles, as soon as they do not meet the criteria for clinical benefit as defined by this protocol. Each patient who does not meet the criteria of clinical benefit after the first cycle with treatment combination 1 will switch to treatment combination 2 (T2). T2 constitutes of 6-mercaptopurine (50 mg once a day) plus valproic acid (300 mg + 600 mg) for 14 days; this will be followed by a 14-day period with no medication. Each cycle duration is 28 days. Patients will be further eligible to continue this regimen/combination for as long as they experience clinical benefit, otherwise they will be withdrawn from the study as soon as they do not meet the criteria for clinical benefit as defined by this protocol.

There will be 8 patients allocated for the treatment combination 1 with HU + VPA and up to 8 patients allocated for the treatment combination 2 with 6MP + VPA. For each of the two treatment combinations, if one or more patients, of 8, experience clinical benefit* the group will be expanded with 16 more patients in Part B. Part B consists of two cohort expansions where the setup is identical to part A, one for HU + VPA and one for 6MP + VPA, 16 patients in each, in total up to 32 new patients.

In part B, the same principles will apply for response, withdrawal and allocation from HU+ VPA to 6MP + VPA. Patients treated with combination 1, who do not experience clinical benefit or experience unacceptable, unmanageable toxicity after cycle 1, will not be eligible to continue on this regimen, and they will be allocated to combination 2. It is expected that cohort expansion of combination 2 will proceed slower than cohort expansion for combination 1.

If 5 or more patients of the total of 24 (part A (n=8) + part B (n=16)) experience clinical benefit, there will be considered a phase II/III expansion cohort for further effect assessment.

The treatment duration in all groups can last to up 6 cycles in total, each cycle lasts for 28 days. The rationale for the flow in the study aims to ensure that the patients do not undergo prolonged periods with excessive and ineffective treatment. Assessment of treatment response consecutively after each cycle will guide the treating physician to swiftly change the treatment combination or withdraw the patient from the study accordingly.

The switch to a second treatment combination as a part of the study ensures that more therapy options are available for, potentially, all patients who enroll in the trial.

The enrollment is stopped when 8+16 patients with HU +VPA are treated, or if 8+16 patients are treated with 6MP + VPA. Patients will switch over to 6MP +VPA, if lack of clinical benefit. Some dose modifications are allowed when indicated according to the protocol. At screening and during the study treatment, tumor debulking with HU + 6MP is required for 5 to 7 days to reduce WBC to less than 25×10*9/L (<20% blasts in the peripheral blood), before each cycle, HU + VPA, or 6MP + VPA. Tumor debulking with HU + 6MP may be repeated ahead of every cycle (for both treatment combinations), and in the treating physician's discretion, if the patient tolerates this.

The objectives of this study include:

  • To determine the safety and tolerability of the treatment combinations of hydroxyurea + valproic acid, and 6-mercaptopurine + valproic acid administered at established clinical doses
  • To establish the preliminary efficacy of the treatment combination of hydroxyurea and valproic acid administered at established clinical doses
  • To establish the preliminary efficacy of the treatment combination of 6-mercaptopurine and valproic acid administered at established clinical doses
  • To evaluate changes in patients performance status for baseline and during the study period

The adaptive study design is based on a Simon two-stage model of expanding cohorts. This model, tested in the TAPUR, DRUP and Impress-Norway studies, has been designed to effectively test a set of drugs using a minimum of number of patients (see also Chapter 9 on Statistics).

Each arm (A1, A2, B1 and B2) will be monitored using a Simon-like two-stage 'admissible' monitoring plan to identify patients with evidence of clinical benefit. Both arms in part A will enroll 8 participants, and will be considered positive if ≥1 patient show clinical benefit after at least 28 days on treatment (for each arm). In case of a positive part A (arm A1 and A2, separately), part B (arm B1 and B2, separately) will be initiated enrolling 16 additional participants in each arm into the cohort.

If there are 0 patients with "clinical benefit" (as defined by this protocol) among the first 8 participants in an arm, then the respective arm will not proceed to expansion. Otherwise, an additional 16 participants will be included in each cohort expansion (B1 and B2, respectively). Four or fewer responses out of 24 will suggest a lack of activity, while 5 or more responses will suggest that further investigation of the drug in a phase 3 clinical trial is warranted.

  • Study duration: 5 years
  • Treatment duration: up to 6 months for each treatment combination
  • Visit frequency: every 7 days (if applicable, during the first cycle), thereafter every 28 days
Being tested
Hydroxyurea, Hydroxycarbamide, Valproic acid, 6-Mercaptopurine (6-MP)
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hydroxyurea, HydroxycarbamideDrug

    Also called Hydroxyurea Medac

    Hydroxyurea (HU/hydroxycarbamide) is a hydroxylated analogue of urea which prevents DNA synthesis by inhibiting the activity of ribonucleotide reductase (RNR). HU has been used to treat a variety of diseases. As an antineoplastic drug, HU has some advantages. It may be used by ambulatory patients and has relatively few side effects, which are relieved almost immediately after withdrawal of the drug. The drug is readily absorbed from the gastrointestinal tract following oral administration. At present, HU has an important role as standard of care for treating hyperleukocytosis in chronic and acute myeloid leukemia.

  • Valproic acidDrug

    Also called Orfiril Long depot, Belvo, Depakote, Dyzantil

    Valproic acid (VPA) has been used clinically as an anticonvulsant and mood-stabilizing drug. During the last two decades, VPA has been described as a histone deacetylase (HDAC) inhibitor and gained increased interest for use in cancer therapy. VPA is administered orally with available routine measurements of serum levels and has a low toxicity profile.

  • 6-Mercaptopurine (6-MP)Drug

    Also called Puri-Nethol

    In 1953, 6-MP was an approved antileukemic agent resulting in remissions in children with acute lymphocytic leukemia (ALL). After adding 6-MP to methotrexate and prednisolone in the treatment regimen, the one-year mean survival of children with ALL was increased from 29% to 50%. 6-MP, even about 70 years after its discovery, remains the standard maintenance therapy once the children are in complete remission.

Study groups in NCT06199557
Study groupRoleWhat they receive
Hydroxyurea (HU) + Valproic Acid (VPA) part 1Active comparatorCombination treatment 1 (T1): hydroxyurea + valproic acid, combination treatment 2 (T2): 6-mercaptopurine + valproic acid. Each patient enrolled will receive at least one cycle with T1: hydroxyurea and valproic acid. The 1st cycle in the study always constitutes of hydroxyurea (1000 mg twice a day) plus valproic acid (300 mg + 600 mg) for 14 days; then 14 days with no medication. Each cycle duration is 28 days. Patients who do not experience clinical benefit after 1st cycle, or experience unacceptable and unmanageable toxicity after 1st cycle, will not be eligible to continue on this regimen and they will be allocated to treatment combination 2. T2 constitutes of 6-mercaptopurine ( 50 mg once a day) plus valproic acid 300 mg + 600 mg ) for 14 days; followed by 14 days with no medication. Each cycle duration is 28 days.
Receives: Drug: Hydroxyurea, Hydroxycarbamide; Drug: Valproic acid; Drug: 6-Mercaptopurine (6-MP)
Hydroxyurea (HU) + Valproic Acid (VPA) part 2Active comparatorPart B consists of two cohort expansions where the setup is identical to part A: one for HU + VPA and one for 6-MP + VPA, 16 patients in each, in total 32 new patients. In part B the same principles will apply for response, withdrawal and allocation from HU+ VPA to 6-MP + VPA. The treatment duration in all arms can last to up 6 cycles in total. Each cycle duration is 28 days.
Receives: Drug: Hydroxyurea, Hydroxycarbamide; Drug: Valproic acid; Drug: 6-Mercaptopurine (6-MP)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of the treatment combinations of hydroxyurea + valproic acid, and 6-mercaptopurine + valproic acid administered at established clinical doses.

    Safety and tolerability assessed by monitoring the incidence, frequency, and severity of AEs by using CTCAE v5.0, including evaluation of the following:

    • DLTs
    • Physical examinations
    • Clinical laboratory blood samples

    Measured: Evaluation every 4th week, i.e. after each treatment cycle.

  2. Preliminary efficacy of the treatment combination of hydroxyurea and valproic acid administered at established clinical doses.

    Clinical benefit in patients receiving hydroxyurea in combination with valproic acid.

    Clinical benefit in patients receiving 6-mercaptopurine in combination with valproic acid.

    Clinical benefit, in this protocol, is defined as stable disease, partial response (decrease of bone marrow blast percentage to between 5% to 25% and decrease of pre-treatment bone marrow blast percentage by at least 50%), or better response [European Leukemia Net (ELN) 2022 response criteria in AML], and/or stable or improved ECOG performance status.

    Measured: Evaluation every 4th week, i.e. after each treatment cycle.

  3. Changes in patients performance status from baseline and during the study period.

    Baseline and longitudinal ECOG performance status of the patient (Eastern Cooperative Oncology Group). The ECOG performance status scale is best at 0 (fully active, able to carry on all pre-disease performance without restriction), and worst at 5 (dead).

    Measured: Evaluation at baseline, i.e. before onset treatment, after 4 weeks on treatment (i.e.after first cycle), and every 4th week to a total of 24 weeks. (i.e. after each treatment cycle, up to a total of 6 cycles).

Secondary outcomes (8)

  1. Clinical benefit.

    The percentage of patients with clinical benefit (as described over) in each group (A1, A2, B1, B2).

    Measured: After 3 and 6 cycles (i.e. after 3 and 6 months from the treatment onset).

  2. Duration of clinical benefit.

    The duration of clinical benefit (in days), in each group (A1, A2, B1, B2).

    Measured: During the treatment period of 6 months, and during follow-up, up to 6 months after end treatment.

  3. Time to progression.

    The time to progression (days), in each group (A1, A2, B1, B2).

    Measured: From the treatment onset, during the treatment period of 6 months, and during follow-up, up to 6 months after end treatment.

  4. Changes in reported Quality of Life (QoL) compared to baseline.

    Use of health-related quality of life questionnaires:

    • EQ -5D-5L
    • QLQ-C30
    • NCI- PRO-CTCAE

    Measured: At baseline, i.e. before onset treatment, after 4 weeks on treatment (i.e.after first cycle), and after each treatment cycle (every 4th week).

  5. Survival analyses, ORR.

    The overall response rate (ORR) defined as the percentage of patients with a response of complete remission (CR), complete remission with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR), or no response, all as assessed by ELN response criteria 2022, in each group (A1, A2, B1, B2).

    Measured: After 3 and 6 cycles (i.e. after 3 and 6 months from the treatment onset).

  6. Survival analyses, OS.

    The overall survival (OS), in each group (A1, A2, B1, B2).

    Measured: From the treatment onset, during the treatment period of 6 months, and during follow-up, up to 6 months after end-treatment.

  7. Hospitalization rate per month per patient.

    The number of hospital admissions per month before, during, and after study investigation.

    Measured: Before the treatment onset, during the treatment period of 6 months, and during follow-up, up to 6 months after end treatment.

  8. Transfusion rate per month per patient.

    The number of blood-/platelet transfusions per month, during and after study investigation.

    Measured: Before the treatment onset, during the treatment period of 6 months, and during follow-up, up to 6 months after end treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2024
  2. Study start23 May 2024
  3. Primary completion30 Nov 2025 (estimated)
  4. Study completion30 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
This a two-part, open-label phase 1/2 study that will include clinical sites in Norway and other Nordic countries. The study consists of part A and part B.
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06199557
Sponsor's protocol ID
HUVPA_6MPVPA
Acronym
HUVAMER
Status last verified
Jun 2025
First submitted
12 Dec 2023
Last updated
29 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The data are shared with the research group to which the PI and study staff belong to. If relevant, data can be shared with the network. All data that are to be shared will be fully anonymized and followed the relevant guidelines.

Publications

  • Dohner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, Ebert BL, Fenaux P, Godley LA, Hasserjian RP, Larson RA, Levine RL, Miyazaki Y, Niederwieser D, Ossenkoppele G, Rollig C, Sierra J, Stein EM, Tallman MS, Tien HF, Wang J, Wierzbowska A, Lowenberg B. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022 Sep 22;140(12):1345-1377. doi: 10.1182/blood.2022016867.

    PubMed 35797463

  • Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med. 1999 Sep 30;341(14):1051-62. doi: 10.1056/NEJM199909303411407. No abstract available.

    PubMed 10502596

  • Musialek MW, Rybaczek D. Hydroxyurea-The Good, the Bad and the Ugly. Genes (Basel). 2021 Jul 19;12(7):1096. doi: 10.3390/genes12071096.

    PubMed 34356112

  • Fredly H, Gjertsen BT, Bruserud O. Histone 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. Clin Epigenetics. 2013 Jul 30;5(1):12. doi: 10.1186/1868-7083-5-12.

    PubMed 23898968

  • Leitch C, Osdal T, Andresen V, Molland M, Kristiansen S, Nguyen XN, Bruserud O, Gjertsen BT, McCormack E. Hydroxyurea synergizes with valproic acid in wild-type p53 acute myeloid leukaemia. Oncotarget. 2016 Feb 16;7(7):8105-18. doi: 10.18632/oncotarget.6991.

    PubMed 26812881

  • Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21.

    PubMed 19230772

  • Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F, Cortes J, Wierda WG, Ouzounian S, Quezada A, Pierce S, Estey EH, Issa JP, Kantarjian HM, Garcia-Manero G. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood. 2007 Oct 1;110(7):2302-8. doi: 10.1182/blood-2007-03-078576. Epub 2007 Jun 27.

    PubMed 17596541

  • Chateauvieux S, Morceau F, Dicato M, Diederich M. Molecular and therapeutic potential and toxicity of valproic acid. J Biomed Biotechnol. 2010;2010:479364. doi: 10.1155/2010/479364. Epub 2010 Jul 29.

    PubMed 20798865

  • Tassara M, Dohner K, Brossart P, Held G, Gotze K, Horst HA, Ringhoffer M, Kohne CH, Kremers S, Raghavachar A, Wulf G, Kirchen H, Nachbaur D, Derigs HG, Wattad M, Koller E, Brugger W, Matzdorff A, Greil R, Heil G, Paschka P, Gaidzik VI, Gottlicher M, Dohner H, Schlenk RF. Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients. Blood. 2014 Jun 26;123(26):4027-36. doi: 10.1182/blood-2013-12-546283. Epub 2014 May 5.

    PubMed 24797300

  • Elion GB. Historical background of 6-mercaptopurine. Toxicol Ind Health. 1986 Sep;2(2):1-9. doi: 10.1177/074823378600200201. No abstract available.

    PubMed 3538499

  • BURCHENAL JH, MURPHY ML, ELLISON RR, SYKES MP, TAN TC, LEONE LA, KARNOFSKY DA, CRAVER LF, DARGEON HW, RHOADS CP. Clinical evaluation of a new antimetabolite, 6-mercaptopurine, in the treatment of leukemia and allied diseases. Blood. 1953 Nov;8(11):965-99. No abstract available.

    PubMed 13105700

  • Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011 Feb 10;29(5):487-94. doi: 10.1200/JCO.2010.30.1820. Epub 2011 Jan 10.

    PubMed 21220605

  • Estey E. Acute myeloid leukemia and myelodysplastic syndromes in older patients. J Clin Oncol. 2007 May 10;25(14):1908-15. doi: 10.1200/JCO.2006.10.2731.

    PubMed 17488990

  • Hiddemann W, Kern W, Schoch C, Fonatsch C, Heinecke A, Wormann B, Buchner T. Management of acute myeloid leukemia in elderly patients. J Clin Oncol. 1999 Nov;17(11):3569-76. doi: 10.1200/JCO.1999.17.11.3569.

    PubMed 10550156

  • Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysak D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. doi: 10.1200/JCO.2011.38.9429. Epub 2012 Jun 11.

    PubMed 22689805

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Hydroxyurea, Hydroxycarbamide, Valproic acid and 6-Mercaptopurine (6-MP) in people with Acute Myeloid Leukemia, Adult and Myelodysplastic Syndromes, Adult, run by Haukeland University Hospital at 1 site in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bjørn Tore Gjertsen, MD, PhD (004741566248, bjorn.tore.gjertsen@helse-bergen.no), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability of the treatment combinations of hydroxyurea + valproic acid, and 6-mercaptopurine + valproic acid administered at established clinical doses. (time frame: Evaluation every 4th week, i.e. after each treatment cycle.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06199557, which also lists 58 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2025.

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