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AML, AdultPhase 2HO171NCT06014489

A Trial to Assess Cobicistat Boosted Venetoclax in Combination With Azacitidine in Adult Patients With Newly Diagnosed AML

A Phase 2 study testing azacitidine, Venetoclax and Cobicistat in people with AML, Adult, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 19 sites in Netherlands.

Recruiting

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

Sites and contacts
Official record
Search all trials

Trial summary

The treatment of older unfit patients with acute myeloid leukemia (AML) is challenging. The hypomethylating agents (HMA) azacitidine and decitabine have relatively mild side effects and have proven to be feasible for the treatment of older patients and patients with co-morbidities. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
AML, Adult
What is being tested?
azacitidine, Venetoclax and Cobicistat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
142 participants
Where
19 sitesNetherlands
Study dates
17 Jan 2024to Dec 2028
Phase
Phase 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

  • In order to be eligible to participate in this study, a patient must meet all of the following criteria:
  • Patients with: a diagnosis of AML and related precursor neoplasms according to ICC-2022 classification (excluding acute promyelocytic leukaemia) (appendix A). Patients may have had previous treatment with erythropoiesis stimulating agents (ESA) for an antecedent phase of MDS. ESAs must be stopped at least two weeks before registration.
  • Patients 18 years and older who are considered not fit for intensive chemotherapy or who decline the option of intensive chemotherapy.
  • WHO performance status 0, 1 or 2 (appendix E).
  • Leukocytes < 30 x109/L
  • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
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  • Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.
  • Serum bilirubin ≤ 3 x upper limit of normal (ULN), unless considered AML-related or due to Gilbert's syndrome.
  • Alanine transaminase (ALT) ≤ 3 x ULN, unless considered AML-related.
  • Male subjects who are sexually active, must agree, from Study Day 1 until at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.
  • Female subjects must be either postmenopausal defined as: Age >55 years with no menses for ≥12 months, without an alternative medical cause. OR willing and able to use adequate contraception during and until 180 days after the last protocol treatment.
  • Written informed consent.
  • Patient is capable of giving informed consent.
  • Patient agrees not to participate in another interventional study while on treatment without approval of the (co-) Principal Investigator.

Who cannot join

  • A patient who meets any of the following criteria cannot be included in this study:
  • Acute promyelocytic leukemia.
  • Myelodysplastic syndrome (MDS).
  • Patients previously treated for AML or MDS (any anti-leukemic therapy including investigational agents; excluding: 1) erythropoiesis stimulating agents (ESAs); 2) hydroxyurea ((previous treatment with hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis).
  • Diagnosis of any previous or concomitant malignancy is an exclusion criterion:
  • except when the patient successfully completed treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 24 months prior to registration;
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  • except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix.
  • Blast crisis of chronic myeloid leukemia.
  • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.).
  • Cardiac dysfunction as defined by:
  • Myocardial infarction within the last 3 months of study entry, or
  • Reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram, or
  • Unstable angina or New York Heart Association (NYHA) grade IV congestive heart failure (see Appendix G), or
  • Unstable cardiac arrhythmias.
  • History of stroke or intracranial haemorrhage within 6 months prior to registration.
  • Symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement).
  • History of non-compliance to medical regimens or considered unreliable with respect to compliance.
  • 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 hydroxyurea.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  • Unreplaceable use of strong inhibitors or inducers of CYP3A or CYP3A/p-GP substrates with a narrow therapeutic window (e.g. cobicistat or ritonavir for HIV treatment). Please check with Appendix I.
  • Intolerability, contra-indication or allergy to one of the study drugs.

Trial locations and contacts

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

Gerwin Huls, prof contact

+3150 361 2354

g.huls@umcg.nl

19 sites in 1 country

Netherlands19 sites, 19 recruiting
  • NL-Den Bosch-JBZ

    's-Hertogenbosch

    A.H.E. Herbers, Dr.

    Recruiting
  • NL-Amersfoort-MEANDERMC

    Amersfoort

    M.F. Corsten, Dr.

    Recruiting
  • NL-Amsterdam-AUMC

    Amsterdam

    C. Alhan, Dr.

    Recruiting
  • NL-Amsterdam-OLVG

    Amsterdam

    H. Mooij, Dr.

    Recruiting
  • NL-Arnhem-RIJNSTATE

    Arnhem

    M.L.H. Cuijpers, Dr.

    Recruiting
  • NL-Breda-AMPHIA

    Breda

    R.B. Fiets, Dr.

    Recruiting
  • NL-Dordrecht-ASZ

    Dordrecht

    P.E. Westerweel, Dr.

    Recruiting
  • NL-Eindhoven-CATHARINA

    Eindhoven

    M.J. Cruijsen, Dr.

    Recruiting
  • NL-Eindhoven-MAXIMAMC

    Eindhoven

    L.W. Tick, Dr.

    Recruiting
  • NL-Enschede-MST

    Enschede

    T.J.F. Snijders, Dr.

    Recruiting
  • NL-Groningen-UMCG

    Groningen

    G.A. Huls, Prof. dr.

    Recruiting
  • NL-Leeuwarden-MCL

    Leeuwarden

    B. Franken, Dr.

    Recruiting
  • NL-Leiden-LUMC

    Leiden

    P.A. von dem Borne, Dr.

    Recruiting
  • NL-Maastricht-MUMC

    Maastricht

    C.H.M.J. van Elssen, Dr.

    Recruiting
  • NL-Nieuwegein-ANTONIUS

    Nieuwegein

    O. de Weerdt, Dr.

    Recruiting
  • NL-Nijmegen-CWZ

    Nijmegen

    S. de Jonge, Dr.

    Recruiting
  • NL-Nijmegen-RADBOUDUMC

    Nijmegen

    N.A. de Jonge, Dr.

    Recruiting
  • NL-Den Haag-HAGA

    The Hague

    D. van Lammeren, Dr.

    Recruiting
  • NL-Zwolle-ISALA

    Zwolle

    T.T. de Waal, Dr.

    Recruiting

Other trials in Netherlands

About this study

Official title: A Single Arm Phase II Trial to Assess Cobicistat Boosted Venetoclax in Combination With Azacitidine (sc) in Adult Patients With Newly Diagnosed Acute Myeloid Leukaemia (AML) Who Are Not Considered Candidates for Intensive Treatment Regimens

The treatment of older unfit patients with acute myeloid leukemia (AML) is challenging. The hypomethylating agents (HMA) azacitidine and decitabine have relatively mild side effects and have proven to be feasible for the treatment of older patients and patients with co-morbidities. Currently, venetoclax added to an HMA agent is the new standard of treatment. Since this new standard comes with a substantial societal financial burden, there is a rational to optimize the venetoclax dosing schedule. The CYP3A4 inhibitor cobicistat (COBI) can be used to increase venetoclax exposure, thereby allowing to reduce the dose of venetoclax and thus costs substantially.

Conditions
AML, Adult
Being tested
azacitidine, Venetoclax, Cobicistat
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • azacitidineDrug

    during run-in and extention phase: from Cycle 1 until relapse

  • VenetoclaxDrug

    during run-in and extention phase: from Cycle 1 until relapse

  • CobicistatDrug

    during run-in phase: from cycle 2 until relapse

    during extension phase: from cycle 1 until relapse

Study groups in NCT06014489
Study groupRoleWhat they receive
single arm arm extension phaseExperimentalprior to the extention phase, there is a run-in phase with (n= 20 patients of 142 total) with the same study scheme, except that cobicistat is added from cycle 2 onwards to the treatment instead of during cycle 1
Receives: Drug: azacitidine; Drug: Venetoclax; Drug: Cobicistat

What is being measured

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

  1. Pharmacokinetic equivalence of cobicistat boosted venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2).venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2).

    run-in phase

    Measured: 6-8 months

  2. Overall survival (OS).

    extension phase

    Measured: 48 months

Secondary outcomes (20)
  1. Venetoclax and cobicistat CL, Cmax, Tmax, Cmin and AUC0-24.

    run-in phase

    Measured: 6-8 months

  2. Complete remission (CR) rate defined as CR as best response during or at completion of the treatment, as determined by the Investigator, based on the European LeukemiaNet (ELN2022) recommended response criteria (see Appendix B).

    extension phase

    Measured: 48 months

  3. CR with incomplete hematologic recovery (CRi) rate, based on the European LeukemiaNet (ELN2022) recommended response criteria (see Appendix B).

    extension phase

    Measured: 48 months

  4. CR and CR with incomplete hematologic recovery (CRi) rate, based on the European LeukemiaNet (ELN2022) recommended response criteria (see Appendix B).

    extension phase

    Measured: 48 months

  5. CR with partial hematologic recovery (CRh) rate, based on ELN 2022 recommendations.

    extension phase

    Measured: 48 months

  6. CR and CR with partial hematologic recovery (CRh) rate, based on ELN 2022 recommendations.

    extension phase

    Measured: 48 months

  7. CR or CR/CRi or CR/CRh without minimal residual disease (flow and or molecular) (CRMRD- or CR/CRiMRD- or CR/CRhMRD-).

    extension phase

    Measured: 48 months

  8. Morphologic leukemia-free state (MLFS) rate, based on ELN2022 recommendations.

    extension phase

    Measured: 48 months

  9. Event free survival (EFS).

    extension phase

    Measured: 48 months

  10. Relapse-free survival (RFS).

    extension phase

    Measured: 48 months

  11. Incidence and severity of adverse events according to CTCAE version 5.0.

    extension phase

    Measured: 48 months

  12. Early (30-day and 60-day) mortality (in general, non-leukemic).

    extension phase

    Measured: 48 months

  13. Time to next cycle, defined as the time from the start of the cycle until the start of the next cycle.

    extension phase

    Measured: 48 months

  14. OS of AZA/VEN/COBI treated patients in comparison with a real-world data cohort treated during the same time period and monitored by the Dutch Cancer registry.

    extension phase

    Measured: 48 months

  15. Prognostic/predictive impact of disease-associated genetic changes at diagnosis.

    extension phase

    Measured: 48 months

  16. Relapse-associated genetic changes (determined at relapse). The average relative dose intensity will be computed and given by categories. The same will be done for treatment deviation.

    extension phase

    Measured: 48 months

  17. Clonal evolution during treatment.

    extension phase

    Measured: 48 months

  18. Exposure-response and exposure-toxicity relation of venetoclax in patients with AML.

    extension phase

    Measured: 48 months

  19. Cost-savings on venetoclax drug costs.

    extension phase

    Measured: 48 months

  20. Adherence to venetoclax and cobicistat.

    extension phase

    Measured: 48 months

Timeline

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

  1. First posted28 Aug 2023
  2. Study start17 Jan 2024
  3. Primary completionDec 2028 (estimated)
  4. Study completionDec 2028 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
the study consists of a run-in phase and an extension phase
Masking
None (open label)
Enrolment
142 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06014489
Sponsor's protocol ID
HO171
Other IDs
2023-505379-61-00, 2023
Acronym
HO171
Status last verified
Sep 2026
First submitted
4 Jul 2023
Last updated
23 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Westra N, Cerro ER, Schilder E, Lub-de Hooge MN, Touw DJ, Kosterink JGW, Chitu DA, Ammatuna E, Klein SK, Westerweel PE, Cuijpers M, Cruijsen M, Corsten MMF, Alhan C, Tick L, Schuringa JJ, Huls G, Woolthuis CM, Oude Munnink TH. Pharmacological boosting of azacitidine/venetoclax in acute myeloid leukemia. Blood Neoplasia. 2026 Mar 12;3(2):100218. doi: 10.1016/j.bneo.2026.100218. eCollection 2026 May.

    PubMed 42007248

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing azacitidine, Venetoclax and Cobicistat in people with AML, Adult, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 19 sites in Netherlands.

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 14 inclusion and 22 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 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Netherlands. 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 phase mean?

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 Gerwin Huls, prof (+3150 361 2354, g.huls@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic equivalence of cobicistat boosted venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2).venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2). (time frame: 6-8 months). The study lists 2 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 NCT06014489, which also lists 1 linked publication.

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 23 Sep 2026.

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