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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

142 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-17

Study Completion Date

2028-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Ivosidenib and Azacitidine With or Without Venetoclax in Adult Patients With Newly Diagnosed IDH1-Mutated AML or MDS/AML Considered Ineligible for Intensive Chemotherapy

NCT07075016

Acute Myeloid Leukemia

RECRUITING PHASE3

Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

NCT03586609

Acute Myeloid Leukemia

RECRUITING PHASE2

Venetoclax + Azacitidine vs. Induction Chemotherapy in AML

NCT04801797

Acute Myeloid Leukemia

RECRUITING PHASE2

Azacitidine, Venetoclax, and Pevonedistat in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT03862157

Acute Myeloid Leukemia Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Chronic Eosinophilic Leukemia, Not Otherwise Specified +13 more

ACTIVE_NOT_RECRUITING PHASE1/PHASE2

Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India

NCT07044687

Acute Myeloid Leukemia

RECRUITING PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

AML, Adult

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

the study consists of a run-in phase and an extension phase

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

single arm arm extension phase

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

Group Type EXPERIMENTAL

azacitidine

Intervention Type DRUG

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

Venetoclax

Intervention Type DRUG

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

Cobicistat

Intervention Type DRUG

during run-in phase: from cycle 2 until relapse

during extension phase: from cycle 1 until relapse

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

azacitidine

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

Intervention Type DRUG

Venetoclax

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

Intervention Type DRUG

Cobicistat

during run-in phase: from cycle 2 until relapse

during extension phase: from cycle 1 until relapse

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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.

Exclusion Criteria

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).
* 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;
* 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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.