NCT06014489

Brief 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. 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
142

participants targeted

Target at P75+ for phase_2

Timeline
22mo left

Started Jan 2024

Typical duration for phase_2

Geographic Reach
1 country

18 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress56%
Jan 2024Mar 2028

First Submitted

Initial submission to the registry

July 4, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 28, 2023

Completed
5 months until next milestone

Study Start

First participant enrolled

January 17, 2024

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2028

Last Updated

January 18, 2024

Status Verified

January 1, 2024

Enrollment Period

4.1 years

First QC Date

July 4, 2023

Last Update Submit

January 17, 2024

Conditions

AML, Adult

Outcome Measures

Primary Outcomes (2)

  • 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

    6-8 months

  • Overall survival (OS).

    extension phase

    48 months

Secondary Outcomes (20)

  • Venetoclax and cobicistat CL, Cmax, Tmax, Cmin and AUC0-24.

    6-8 months

  • 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).

    48 months

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

    48 months

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

    48 months

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

    48 months

  • +15 more secondary outcomes

Study Arms (1)

single arm arm extension phase

EXPERIMENTAL

prior 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

Drug: azacitidineDrug: VenetoclaxDrug: Cobicistat

Interventions

azacitidineDRUG

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

single arm arm extension phase
VenetoclaxDRUG

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

single arm arm extension phase
CobicistatDRUG

during run-in phase: from cycle 2 until relapse during extension phase: from cycle 1 until relapse

single arm arm extension phase

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).
  • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
  • 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.

You may not qualify if:

  • 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 (hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis).
  • 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;
  • 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).
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

NL-Amersfoort-MEANDERMC

Amersfoort, Netherlands

NOT YET RECRUITING

NL-Amsterdam-OLVG

Amsterdam, Netherlands

NOT YET RECRUITING

NL-Amsterdam-VUMC

Amsterdam, Netherlands

NOT YET RECRUITING

NL-Arnhem-RIJNSTATE

Arnhem, Netherlands

NOT YET RECRUITING

NL-Breda-AMPHIA

Breda, Netherlands

NOT YET RECRUITING

NL-Dordrecht-ASZ

Dordrecht, Netherlands

NOT YET RECRUITING

NL-Eindhoven-CATHARINA

Eindhoven, Netherlands

NOT YET RECRUITING

NL-Eindhoven-MAXIMAMC

Eindhoven, Netherlands

NOT YET RECRUITING

NL-Enschede-MST

Enschede, Netherlands

NOT YET RECRUITING

NL-Groningen-UMCG

Groningen, Netherlands

RECRUITING

NL-Leeuwarden-MCL

Leeuwarden, Netherlands

NOT YET RECRUITING

NL-Leiden-LUMC

Leiden, Netherlands

NOT YET RECRUITING

NL-Maastricht-MUMC

Maastricht, Netherlands

NOT YET RECRUITING

NL-Nieuwegein-ANTONIUS

Nieuwegein, Netherlands

NOT YET RECRUITING

NL-Nijmegen-CWZ

Nijmegen, Netherlands

NOT YET RECRUITING

NL-Rotterdam-ERASMUSMC

Rotterdam, Netherlands

NOT YET RECRUITING

NL-Den Haag-HAGA

The Hague, Netherlands

NOT YET RECRUITING

NL-Zwolle-ISALA

Zwolle, Netherlands

NOT YET RECRUITING

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

AzacitidinevenetoclaxCobicistat

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesCarbamatesAcids, AcyclicCarboxylic AcidsThiazolesSulfur CompoundsAzoles

Central Study Contacts

Gerwin Huls, prof

CONTACT

+3150 361 2354g.huls@umcg.nl

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: the study consists of a run-in phase and an extension phase
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 4, 2023

First Posted

August 28, 2023

Study Start

January 17, 2024

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2028

Last Updated

January 18, 2024

Record last verified: 2024-01

Locations

NL(18)