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Acute Myeloid LeukemiaPhase 2VenExNCT04267081

Study of Venetoclax in Combination With Azacytidine in AML Patients Selected Using Ex Vivo Drug Sensitivity Screening

A Phase 2 study testing Venetoclax in people with Acute Myeloid Leukemia, run by Helsinki University Central Hospital at 1 site in Finland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multi center two-stage, two-arm, open label phase II study of venetoclax in combination with azacytidine in acute myeloid leukemia patients selected for therapy with ex vivo venetoclax sensitivity screening. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
1 siteFinland
Study dates
12 Feb 2020to 28 Feb 2024
Phase
Phase 2
Are there results?
None posted in the registry

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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent
  • Patients who present with one of the following (except acute promyelocytic leukemia):
  • De novo or secondary AML patients who are non-fit for standard induction therapy (see below)
  • Relapsed or refractory AML patients following at least 1 line of prior therapies (see below)
  • Ex vivo sensitivity testing performed to assess venetoclax sensitivity
  • Validation cohort: All participants are treated with venetoclax+azacitidine irrespective of the ex vivo screening results.
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  • Study cohort: Only the participants exhibiting ex vivo sensitivity to venetoclax are included to study therapy.
  • Participant must have ECOG Performance status ≤ 2 for participants ≥ 75 years of age OR ≤ 3 for participants ≥ 18 to 74 years of age
  • Leukocyte count < 25 x10E9/l. Hydroxyurea use is permitted to meet this criterion.
  • Participant must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined by the Cockcroft Gault formula.
  • Participant must have adequate liver function as demonstrated by
  • alanine aminotransferase (ALT) ≤ 4.0 × ULN
  • bilirubin ≤ 1.5 × ULN
  • Specific inclusion criteria for participants non-fit for standard chemotherapy
  • Participant must be:
  • ≥ 70 years of age OR ≥ 18 to 69 years of age and ineligible for intensive chemotherapy meeting at least one of the criteria following:
  • Clinically significant comorbidities, reflected at least 1 of:
  • Left ventricular ejection fraction (LVEF) < 50%.
  • Lung diffusion capacity for carbon monoxide (DLCO) ≤ 65% of expected.
  • Forced expiratory volume in 1 second (FEV1) ≤ 65% of expected.
  • Chronic stable angina or congestive heart failure controlled with medication.
  • Alanine aminotransferase (ALT) 3.0-4.0 × ULN
  • Other contraindication(s) to anthracycline therapy (must be documented)
  • Adverse risk karyotype associated with poor outcome with standard chemotherapy
  • Patient's refusal from intensive chemotherapy
  • Specific inclusion criteria for relapsed patients
  • Participant must be ≥ 55 years of age with non-CBF AML relapse OR ≥ 18 of age and meeting at least one of the criteria following:
  • Not candidate for intensive chemotherapy (see the criteria 8.)
  • The duration of remission < 12 months.
  • Relapse after allogeneic transplantation.
  • 2nd (or higher) relapse.
  • Specific inclusion criteria for refractory patients The patients who fail to achieve a complete or partial remission after induction chemotherapy (two cycles of chemotherapy containing cytarabine or clofarabine, in compilation with topoisomerase II inhibitor (e.g. anthracycline or mitoxantrone)

Who cannot join

  • Participant has acute promyelocytic leukemia (APL)
  • The leukemic cell content (blast percentage) in bone marrow/peripheral blood (depending which is used for drug sensitivity testing) is ≤ 10 %
  • ECOG >3 (see also inclusion criteria 4)
  • Participant has known CNS involvement with AML (note: CSF or radiological investigations are not required without clinical suspicion)
  • Participant with known HIV infection or active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection that is not controlled with anti-viral medication.
  • Participant has cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which participants are comfortable at rest but ordinary physical activity results in palpitations, fatigue, dyspnea, or anginal pain.
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  • Evidence of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participation in this study (including but not limited to):
  • Participant has a chronic respiratory disease that requires continuous oxygen use
  • Systemic uncontrolled infection requiring therapy (viral, bacterial or fungal)
  • Malabsorption syndrome or other condition that precludes enteral route of administration.
  • Uncontrolled GVHD.
  • Participant has a history of other malignancies prior to study entry, with the exception of previous malignancy treated with curative intent.

Trial locations and contacts

1 site in 1 country.

Finland1 site

  • HelsinkiUCH

    Helsinki, Uusimaa, 00029

Other trials in Finland

About this study

Official title: Two-stage, Two-arm, Open-Label Phase II Study of Venetoclax in Combination With Azacytidine in Acute Myeloid Leukemia Patients Selected Using Ex Vivo Drug Sensitivity Screening

This is a multi center two-stage, two-arm, open label phase II study of venetoclax in combination with azacytidine in acute myeloid leukemia patients selected for therapy with ex vivo venetoclax sensitivity screening. This study will characterize the usability of ex vivo drug sensitivity testing for patient selection for selecting the responsive patients for venetoclax therapy. The exploratory study will aim to find novel combinations for overcoming resistance as well as finding/validating biomarkers for both sensitivity and resistance.

Being tested
Venetoclax
Keywords
AML, Venetoclax, Azacytidine, Drug Sensitivity Screening
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.

  • VenetoclaxDrug

    Also called Ex vivo drug sensitivity testing

    Ex vivo venetoclax sensitivity testing is used for patient selection.

Study groups in NCT04267081
Study groupRoleWhat they receive
Arm 1 (de novo AML)ExperimentalThis arm will recruit the patients with de novo AML unfit for conventional chemotherapy. In validation cohort all the participants will receive azacytidine-venetoclax. In study cohort the patients with ex vivo resistance to venetoclax will be excluded from the study therapy. All patients in validation and study cohorts (ARM1 and ARM2) will receive azacytidine and venetoclax. The purpose for the validation cohort is to validate the specificity and sensitivity of the ex vivo drug testing. Patients exhibiting ex vivo sensitivity and receiving azacytidine-venetoclax in validation cohort are analyzed also for study cohort.
Receives: Drug: Venetoclax
Arm 2 (relapsed, refractory or secondary AML)ExperimentalThis arm will recruit the patients with relapsed, refractory or secondary AML. In validation cohort all the participants will receive azacytidine-venetoclax. In study cohort the patients with ex vivo resistance to venetoclax will be excluded from the study therapy. All patients in validation and study cohorts (ARM1 and ARM2) will receive azacytidine and venetoclax. The purpose for the validation cohort is to validate the specificity and sensitivity of the ex vivo drug testing. Patients exhibiting ex vivo sensitivity and receiving azacytidine-venetoclax in validation cohort are analyzed also for study cohort.
Receives: Drug: Venetoclax

What is being measured

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

  1. Complete remission (CR)/complete remission rate with incomplete hematologic recovery (CRi) rate in study cohort after three cycles.

    Measured: The bone marrow is examined at the end of Cycle 3. Each cycle is 28 days.

Secondary outcomes (2)

  1. The correlation of ex vivo venetoclax sensitivity and specific responses: Overall Survival (OS), Duration of Response (DOR), Event-free Survival (EFS) and Minimal Residual Disease (MRD) status.

    Measured: Through study completion, an average of 3 years

  2. The correlation of venetoclax blood concentrations to specific responses: Overall Survival (OS), Duration of Response (DOR), Event-free Survival (EFS) and Minimal Residual Disease (MRD) status.

    Measured: Through study completion, an average of 3 years

Timeline

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

  1. First posted12 Feb 2020
  2. Study start12 Feb 2020
  3. Primary completion28 Feb 2024
  4. Study completion28 Feb 2024

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
Non-randomised
Intervention model
Parallel groups
Model description
This is a multicenter two-stage, two-arm, open label phase II study.
Masking
None (open label)
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04267081
Sponsor's protocol ID
FLG-V001
Acronym
VenEx
Status last verified
Sep 2024
First submitted
7 Feb 2020
Last updated
4 Sep 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kytola S, Vanttinen I, Ruokoranta T, Partanen A, Holopainen A, Saad J, Kuusisto MEL, Koskela S, Raty R, Itala-Remes M, Vastrik I, Suvela M, Parsons A, Porkka K, Wennerberg K, Heckman CA, Jalkanen T, Huttunen T, Ettala P, Rimpilainen J, Siitonen T, Pyorala M, Kuusanmaki H, Kontro M. Ex vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trial. Blood. 2025 Jan 23;145(4):409-421. doi: 10.1182/blood.2024024968.

    PubMed 39357056

  • Kuusanmaki H, Kytola S, Vanttinen I, Ruokoranta T, Ranta A, Huuhtanen J, Suvela M, Parsons A, Holopainen A, Partanen A, Kuusisto MEL, Koskela S, Raty R, Itala-Remes M, Vastrik I, Dufva O, Siitonen S, Porkka K, Wennerberg K, Heckman CA, Ettala P, Pyorala M, Rimpilainen J, Siitonen T, Kontro M. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia. Haematologica. 2023 Jul 1;108(7):1768-1781. doi: 10.3324/haematol.2022.281692.

    PubMed 36519325

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax in people with Acute Myeloid Leukemia, run by Helsinki University Central Hospital at 1 site in Finland.

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 32 inclusion and 12 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: finished, as of the sponsor's last update on 4 Sep 2024. 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 Finland. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete remission (CR)/complete remission rate with incomplete hematologic recovery (CRi) rate in study cohort after three cycles. (time frame: The bone marrow is examined at the end of Cycle 3. Each cycle is 28 days.). 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 NCT04267081, which also lists 2 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 4 Sep 2024.

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