AzTrials
AzTrials

Chronic Myeloid LeukemiaPhase 2AVENHIRNCT05768711

Azacitidine Combined With Venetoclax in Patients With Higher-risk Chronic Myelomonocytic Leukemia (AVENHIR)

A Phase 2 study testing Venetoclax in people with Chronic Myeloid Leukemia, run by Groupe Francophone des Myelodysplasies at 24 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Open-label phase II, single arm, multicenter study with safety run-in to evaluate the efficacy and safety of Azacitidine combined with Venetoclax in patients with higher-risk chronic myelomonocytic leukemia Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukemia
What is being tested?
Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
24 sitesFrance
Study dates
4 Oct 2023to Oct 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

  • Age 18 and older.
  • CMML diagnosis according to ICC 2022 criteria.
  • Intermediate-2 or high risk according to the molecular CMML Prognostic Scoring System (CPSS-mol) at study entry. In patients treated with HY at screening, the white blood count (WBC) prior to introduction of HY will be used to compute CPSS-mol. In patients with failed or missing cytogenetics or genetics at screening, cytogenetics and genetics at CMML diagnosis will be used to compute CPSS-mol.
  • No prior treatment with hypomethylaing agents, including Azacitidine, decitabine, SGI-110, AST7227 or CC-486 for CMML or any antecedent condition, including antecedent MDS or auto-immune disease. Prior treatment with Erythropoiesis Stimulating Agents (ESA) is allowed with a > 15 days washout from ESAs. Prior treatment with hydroxyurea (HY) is acceptable. No washout is necessary for those patients but pre-HY WBC will be taken in consideration for CPSS-mol computation.
  • Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale.
  • Adequate organ function including the following:
Show all 18Show fewer
  • total bilirubin < 2 times upper limit of normal (ULN) (except moderate unconjugated hyperbilirubinemia due to intra medullary hemolysis or due to Gilbert syndrome),
  • alanine transaminase (ALT) and aspartate transaminase (AST) < 3 times ULN,
  • Creatinine clearance > 30 mL/min as estimated by the CKD-EPI equation.
  • Signed Informed Consent Form (ICF).
  • Negative pregnancy and adequate contraception (including in male patients) if relevant.
  • A FCBP (female of childbearing potential) for this study is defined as a sexually mature woman who: (1) has not undergone a hysterectomy or bilateral oophorectomy; or (2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
  • A FCBP participating in the study must:
  • Have had 2 negative pregnancy tests as verified by the investigator prior to starting investigational medicinal product (IMP) (unless the screening pregnancy test was done within 72 hours of Cycle 1 Day 1). She must have had agreed to ongoing pregnancy testing during the course of the study and after end of treatment.
  • If sexually active, agree to use, and be able to comply with, highly effective contraception** without interruption, 5 weeks prior to starting IMP, during treatment with IMP (including dose interruptions), and for 3 months after the last dose of IMP.
  • Highly effective contraception is defined in this protocol as the following (information also appears in the ICF): Hormonal contraception (eg, birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation (tying your tubes), or a partner with a vasectomy.
  • Male subjects must have agreed to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane), during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions, and for at least 3 months after the last dose of IMP, even if he had undergone a successful vasectomy.
  • Affiliation to a health insurance system.

Who cannot join

  • Myeloproliferative / myelodysplastic syndrome other than CMML.
  • Bone marrow or peripheral blood blasts (including promonocytes) ≥ 20%. If both local and central review are available and discrepant, the central review will be used.
  • CMML with t(5;12) or PDGFRbeta rearrangement that may be treated with imatinib.
  • Unavailable CPSS-mol at inclusion (WBC prior to HY used to compute CPSS-mol at inclusion in HY-exposed patients) or with a CPSS-mol low or intermediate-1 at study entry.
  • Pregnant or breastfeeding.
  • Serious concomitant systemic disorder, including auto-immune or auto-inflammatory disease requiring > 20 mg/d prednisone equivalent, active bacterial, fungal or viral infection that in the opinion of the investigator, would compromise the safety of the patient and/or his/her ability to complete the study.
Show all 14Show fewer
  • Medical condition requiring therapies with CYP3A strong or moderate inducing or inhibiting activity at screening. All strong or moderate CYP3A inducers should be discontinued 7 days prior to the first dose of study drug. All strong or moderate CYP3A inhibitors should be discontinued 3 days prior to the first dose of study drug. A sample list of CYP3A4 inhibitors and inducers is provided in Appendix F.
  • Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, asymptomatic prostatic cancer not requiring treatment, or other tumors if not active during the last 2 years).
  • Known positive test for human immunodeficiency virus (HIV). Note that HIV testing is not required at Screening.
  • Malabsorption syndrome or other condition that precludes an enteral route of administration.
  • Previous therapy with a hypomethylating agent including azacitidine, decitabine, SGI-110, AST7227 or CC-486 for CMML or any antecedent condition, including antecedent MDS or auto-immune disease.
  • Previous therapy with a BH3 mimetic.
  • Antecedent allogeneic stem cell transplantation (HSCT) for CMML or an antecedent of hematological malignancy. Those never transplanted but eligible for HSCT are eligible for the trial.
  • Subjects referred to in Articles L1121-5 to L1121-8-1 and L1122-1-2 of the Public Health Code.

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

France24 sites

  • CHU d'Amiens

    Amiens, 80054

  • CHU d'Angers

    Angers, 49033

  • Hôpital Avicenne

    Bobigny, 93009

  • Hôpital privé Sévigné

    Cesson-Sévigné, 35510

  • CHU de Grenoble

    Grenoble, 38043

  • Hôpital Claude Huriez

    Lille, 59037

  • CHRU de Limoges

    Limoges, 87046

  • Centre Hospitalier de Mont de Marsan

    Mont-de-Marsan, 40000

  • CHU de Montpellier - Hôpital Saint Eloi

    Montpellier, 34295

  • CHU Hôtel Dieu

    Nantes, 44093

  • Hôpital privé du Confluent SAS

    Nantes, 44277

  • Hôpital Archet 1

    Nice, 06200

  • Hôpital Saint Louis

    Paris, 75010

  • Hôpital Cochin

    Paris, 75014

  • CHU de Bordeaux - Hôpital Haut-Lévêque

    Pessac, 33604

  • Centre hospitalier Lyon sud

    Pierre-Bénite, 69495

  • CHU de Poitiers

    Poitiers, 86021

  • Hôpital NOVO

    Pontoise, 95300

  • Centre Hospitalier Annecy Genevois - Site d'Annecy

    Pringy, 74374

  • Hôpital Pontchaillou

    Rennes, 35033

  • Centre Henri Becquerel

    Rouen, 76038

  • IUCT oncopole

    Toulouse, 31059

  • CHU de Tours - Hôpital Bretonneau

    Tours, 37000

  • Institut Gustave Roussy

    Villejuif, 94800

Other trials in France

About this study

Official title: Phase II Study With Safety run-in of Azacitidine (AZA) Combined With Venetoclax (VEN) in Patients With Higher-risk Chronic Myelomonocytic Leukemia (CMML)

Open-label phase II, single arm, multicenter study with safety run-in to evaluate the efficacy and safety of Azacitidine combined with Venetoclax in patients with higher-risk chronic myelomonocytic leukemia

Read the detailed description

AVENHIR trial is an open-label phase II, single arm, multicenter study with safety run-in to evaluate the efficacy and safety of the combination of Azacitidine and Venetoclax in, hypomethylating agent-naïve, higher-risk chronic myelomonocytic leukemia patients

Being tested
Venetoclax
Keywords
CMML, Azacitidine, Venetoclax
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

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

  • VenetoclaxDrug

    Also called ABT-199

    Combination of Azacitidine and Venetoclax

Study groups in NCT05768711
Study groupRoleWhat they receive
Azacidine+VenetoclaxExperimentalAzacitidine will be administered subcutaneously at the standard dose of 75 mg/m²/d either on days 1-7 or using a 5-2-2 schedule of the 28 day-cycles. Patiens will be exposed to Venetoclax during the first 7 or 14 days of the 28 day-cycles (number of days of Venetoclax determined during the safety run-in phase). At cycle 1, Venetoclax will be given orally with 3-day ramp-up, at 100 mg on day 1, 200 mg on day 2 and 400 mg on days 3 to 7 or 14 of the cycle. At all subsequent cycles, Venetoclax will be given orally at 400 mg on days 1 to 7 or 14 of the cycle. Treatment duration will be 24 months.
Receives: Drug: Venetoclax

What is being measured

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

  1. Safety run-in

    Determination of dose-limiting toxicities within the first two cycles of treatment

    Measured: after 2 cycles of treatment of the safety run-in phase patients (each cycle is 28 days)

  2. Overall response rate

    Overall response encompasses complete remission, partial remission, marrow response and clinical benefit according to protocol-defined criteria modified from MDS/MPN IWG criteria after 3 and 6 cycles of treatment

    Measured: after 3 and 6 cycles of treatment of the phase II patients (each cycle is 28 days)

Secondary outcomes (15)

  1. Complete remission rate

    Complete remission according to protocol-defined criteria modified from MDS/MPN IWG criteria after 3 and 6 cycles of treatment

    Measured: after 3 and 6 cycles of treatment (each cycle is 28 days)

  2. Overall response rate at best response

    Overall response (complete remission, partial remission, marrow response, clinical benefit) according to protocol-defined criteria modified from MDS/MPN IWG criteria at best response

    Measured: through study completion, an average of 5 years

  3. Overall response rate after 3 and 6 cycles of treatment

    Overall response (complete remission, partial remission, marrow response, clinical benefit) according to the DACOTA trial response criteria after 3 and 6 cycles of treatment

    Measured: after 3 and 6 cycles of treatment (each cycle is 28 days)

  4. Duration of response

    Duration of response defined as the time interval between the first date of achievement of any response according to MDS/MPN IWG criteria to progressive disease

    Measured: through study completion, an average of 5 years

  5. Identification and grading of adverse events

    Safety profile, both hematological and non-hematological of treatment (Venetoclax combined with Azacitidine) including identification and grading of adverse events based on NCI CTCAE version 5.0

    Measured: through study completion, an average of 5 years

  6. Overall survival

    Overall survival defined as the time from inclusion until death or end of follow-up

    Measured: through study completion, an average of 5 years

  7. Acute Myeloid Leukemia (AML)-free survival

    AML-free survival defined as the time from inclusion to transformation to AML according to WHO 2016 criteria, death or end of follow-up, whichever occurs first

    Measured: through study completion, an average of 5 years

  8. Progression-free survival

    Progression-free survival defined as the time from inclusion to progressive disease according to MDS/MPN IWG criteria, transformation to AML, death or end of follow-up, whichever occurs first

    Measured: through study completion, an average of 5 years

  9. Event-free survival

    Event-free survival defined as the time from inclusion to failure to achieve any response according to MDS/MPN IWG criteria at the 6-cycle evaluation, occurence of progressive disease according to MDS/MPN IWG criteria, transformaion to AML, or death, whichever occurs first

    Measured: through study completion, an average of 5 years

  10. Cumulative incidence of AML and cumulative risk of death without AML

    Cumulative incidence of AML and cumulative risk of death without AML, considering death and transformation to AML as competing risk

    Measured: through study completion, an average of 5 years

  11. Cumulative incidence of progressive disease or transformation to AML and cumulative risk of death without progression or AML

    Cumulative incidence of progressive disease or transformation to AML and cumulative risk of death without progression or AML

    Measured: through study completion, an average of 5 years

  12. Rate of Hematopoietic Stem Cell Transplantation (HSCT)

    Rate of Hematopoietic Stem Cell Transplantation (HSCT) and post-HSCT ovrall survival and AML-free survival

    Measured: through study completion, an average of 5 years

  13. Survival censoring at Hematopoietic Stem Cell Transplantation (HSCT)

    Overall survival, AML-free survival and progressive-free survival censoring at Hematopoietic Stem Cell Transplantation (HSCT)

    Measured: through study completion, an average of 5 years

  14. Subsequent therapy

    Rate and description of subsequent therapy

    Measured: through study completion, an average of 5 years

  15. Survival censoring to subsequent therapy

    Overall survival, AML-free survival and progressive-free survival censoring at subsequent therapy

    Measured: through study completion, an average of 5 years

Timeline

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

  1. First posted14 Mar 2023
  2. Study start4 Oct 2023
  3. Primary completion16 Jun 2026
  4. Study completionOct 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
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05768711
Sponsor's protocol ID
AVENHIR
Other IDs
2024-514878-53-00, 2021-002007-35
Acronym
AVENHIR
Status last verified
Sep 2026
First submitted
23 Feb 2023
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax in people with Chronic Myeloid Leukemia, run by Groupe Francophone des Myelodysplasies at 24 sites in France.

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 18 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 29 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 24 sites in France. 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?

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?

Safety run-in (time frame: after 2 cycles of treatment of the safety run-in phase patients (each cycle is 28 days)). 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 NCT05768711.

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 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in