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Atsasitidiini yhdistettynä Venetoclaxin kanssa potilailla, joilla on korkean riskin krooninen myelomonosyyttinen leukemia (AVENHIR) (AVENHIR)

torstai 24. syyskuuta 2026 päivittänyt: Groupe Francophone des Myelodysplasies

Vaiheen II tutkimus, jossa atsasitidiinin (AZA) ja venetoklaxin (VEN) käyttö on turvallista potilailla, joilla on korkeamman riskin krooninen myelomonosyyttinen 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

Tutkimuksen yleiskatsaus

Tila

Aktiivinen, ei rekrytointi

Ehdot

Interventio / Hoito

Yksityiskohtainen kuvaus

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

Opintotyyppi

Interventio

Ilmoittautuminen (Arvioitu)

44

Vaihe

  • Vaihe 2

Yhteystiedot ja paikat

Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.

Opiskelupaikat

  • Ranska
      • Amiens, Ranska, 80054
        • CHU d'Amiens
      • Angers, Ranska, 49033
        • CHU d'Angers
      • Bobigny, Ranska, 93009
        • Hôpital Avicenne
      • Cesson-Sévigné, Ranska, 35510
        • Hôpital privé Sévigné
      • Grenoble, Ranska, 38043
        • CHU de Grenoble
      • Lille, Ranska, 59037
        • Hôpital Claude Huriez
      • Limoges, Ranska, 87046
        • CHRU de Limoges
      • Mont-de-Marsan, Ranska, 40000
        • Centre Hospitalier de Mont de Marsan
      • Montpellier, Ranska, 34295
        • CHU de Montpellier - Hôpital Saint Eloi
      • Nantes, Ranska, 44093
        • CHU Hôtel Dieu
      • Nantes, Ranska, 44277
        • Hôpital privé du Confluent SAS
      • Nice, Ranska, 06200
        • Hôpital Archet 1
      • Paris, Ranska, 75014
        • Hôpital Cochin
      • Paris, Ranska, 75010
        • Hôpital Saint Louis
      • Pessac, Ranska, 33604
        • CHU de Bordeaux - Hôpital Haut-Lévêque
      • Pierre-Bénite, Ranska, 69495
        • Centre hospitalier Lyon sud
      • Poitiers, Ranska, 86021
        • CHU de Poitiers
      • Pontoise, Ranska, 95300
        • Hôpital NOVO
      • Pringy, Ranska, 74374
        • Centre Hospitalier Annecy Genevois - Site d'Annecy
      • Rennes, Ranska, 35033
        • Hôpital Pontchaillou
      • Rouen, Ranska, 76038
        • Centre Henri Becquerel
      • Toulouse, Ranska, 31059
        • IUCT oncopole
      • Tours, Ranska, 37000
        • CHU de Tours - Hôpital Bretonneau
      • Villejuif, Ranska, 94800
        • Institut Gustave Roussy

Osallistumiskriteerit

Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.

Kelpoisuusvaatimukset

Opintokelpoiset iät

18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)

Hyväksyy terveitä vapaaehtoisia

Ei

Sukupuolet, jotka voivat opiskella

Kaikki

Kuvaus

Inclusion Criteria:

  1. Age 18 and older.

  2. CMML diagnosis according to ICC 2022 criteria.

  3. 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.

  4. 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.

  5. Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale.

  6. Adequate organ function including the following:

    • 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.

  7. Signed Informed Consent Form (ICF).

  8. 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.

  9. Affiliation to a health insurance system.

Exclusion Criteria:

  1. Myeloproliferative / myelodysplastic syndrome other than CMML.
  2. 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.
  3. CMML with t(5;12) or PDGFRbeta rearrangement that may be treated with imatinib.
  4. 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.
  5. Pregnant or breastfeeding.
  6. 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.
  7. 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.
  8. 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).
  9. Known positive test for human immunodeficiency virus (HIV). Note that HIV testing is not required at Screening.
  10. Malabsorption syndrome or other condition that precludes an enteral route of administration.
  11. 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.
  12. Previous therapy with a BH3 mimetic.
  13. 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.
  14. Subjects referred to in Articles L1121-5 to L1121-8-1 and L1122-1-2 of the Public Health Code.

Opintosuunnitelma

Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.

Miten tutkimus on suunniteltu?

Suunnittelun yksityiskohdat

  • Ensisijainen käyttötarkoitus: Hoito
  • Jako: Ei käytössä
  • Inventiomalli: Yksittäinen ryhmätehtävä
  • Naamiointi: Ei mitään (avoin tarra)

Aseet ja interventiot

Osallistujaryhmä / Arm
Interventio / Hoito
Kokeellinen: Azacidine+Venetoclax

Azacitidine 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.
Lääke: Venetoclax

Combination of Azacitidine and Venetoclax

Muut nimet:
  • ABT-199

Mitä tutkimuksessa mitataan?

Ensisijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Safety run-in
Aikaikkuna: after 2 cycles of treatment of the safety run-in phase patients (each cycle is 28 days)

Determination of dose-limiting toxicities within the first two cycles of treatment
after 2 cycles of treatment of the safety run-in phase patients (each cycle is 28 days)
Overall response rate
Aikaikkuna: after 3 and 6 cycles of treatment of the phase II patients (each cycle is 28 days)

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

Toissijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Complete remission rate
Aikaikkuna: after 3 and 6 cycles of treatment (each cycle is 28 days)

Complete remission according to protocol-defined criteria modified from MDS/MPN IWG criteria after 3 and 6 cycles of treatment
after 3 and 6 cycles of treatment (each cycle is 28 days)
Overall response rate at best response
Aikaikkuna: through study completion, an average of 5 years

Overall response (complete remission, partial remission, marrow response, clinical benefit) according to protocol-defined criteria modified from MDS/MPN IWG criteria at best response
through study completion, an average of 5 years
Overall response rate after 3 and 6 cycles of treatment
Aikaikkuna: after 3 and 6 cycles of treatment (each cycle is 28 days)

Overall response (complete remission, partial remission, marrow response, clinical benefit) according to the DACOTA trial response criteria after 3 and 6 cycles of treatment
after 3 and 6 cycles of treatment (each cycle is 28 days)
Duration of response
Aikaikkuna: through study completion, an average of 5 years

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
through study completion, an average of 5 years
Identification and grading of adverse events
Aikaikkuna: through study completion, an average of 5 years

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
through study completion, an average of 5 years
Overall survival
Aikaikkuna: through study completion, an average of 5 years

Overall survival defined as the time from inclusion until death or end of follow-up
through study completion, an average of 5 years
Acute Myeloid Leukemia (AML)-free survival
Aikaikkuna: through study completion, an average of 5 years

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
through study completion, an average of 5 years
Progression-free survival
Aikaikkuna: through study completion, an average of 5 years

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
through study completion, an average of 5 years
Event-free survival
Aikaikkuna: through study completion, an average of 5 years

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
through study completion, an average of 5 years
Cumulative incidence of AML and cumulative risk of death without AML
Aikaikkuna: through study completion, an average of 5 years

Cumulative incidence of AML and cumulative risk of death without AML, considering death and transformation to AML as competing risk
through study completion, an average of 5 years
Cumulative incidence of progressive disease or transformation to AML and cumulative risk of death without progression or AML
Aikaikkuna: through study completion, an average of 5 years

Cumulative incidence of progressive disease or transformation to AML and cumulative risk of death without progression or AML
through study completion, an average of 5 years
Rate of Hematopoietic Stem Cell Transplantation (HSCT)
Aikaikkuna: through study completion, an average of 5 years

Rate of Hematopoietic Stem Cell Transplantation (HSCT) and post-HSCT ovrall survival and AML-free survival
through study completion, an average of 5 years
Survival censoring at Hematopoietic Stem Cell Transplantation (HSCT)
Aikaikkuna: through study completion, an average of 5 years

Overall survival, AML-free survival and progressive-free survival censoring at Hematopoietic Stem Cell Transplantation (HSCT)
through study completion, an average of 5 years
Subsequent therapy
Aikaikkuna: through study completion, an average of 5 years

Rate and description of subsequent therapy
through study completion, an average of 5 years
Survival censoring to subsequent therapy
Aikaikkuna: through study completion, an average of 5 years

Overall survival, AML-free survival and progressive-free survival censoring at subsequent therapy
through study completion, an average of 5 years

Muut tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Patient reported outcomes
Aikaikkuna: through study completion, an average of 5 years

Patient reported outcomes according to the Myeloproliferative Neoplasm Safety Assessment Form Total Symptom Score which is a 10-item instrument designed to monitor clinically relevant symptoms among patients with myeloproliferative neoplasm. The score has possible range of 0 to 100.
through study completion, an average of 5 years
Exploratory endpoints
Aikaikkuna: through study completion, an average of 5 years

Biomarkers including somatic mutations by targeted sequencing and BH3 profiling CD34+ cells and monocytes
through study completion, an average of 5 years

Yhteistyökumppanit ja tutkijat

Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.

Sponsori

Groupe Francophone des Myelodysplasies

Yhteistyökumppanit

AbbVie

Tutkijat

  • Päätutkija: Raphaël ITZYKSON, MD/PhD, Hôpital Saint Louis
  • Päätutkija: Pierre FENAUX, MD/PhD, Hôpital Saint Louis

Opintojen ennätyspäivät

Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan ​​julkisella verkkosivustolla.

Opi tärkeimmät päivämäärät

Opiskelun aloitus (Todellinen)

Keskiviikko 4. lokakuuta 2023

Ensisijainen valmistuminen (Todellinen)

Tiistai 16. kesäkuuta 2026

Opintojen valmistuminen (Arvioitu)

Sunnuntai 1. lokakuuta 2028

Opintoihin ilmoittautumispäivät

Ensimmäinen lähetetty

Torstai 23. helmikuuta 2023

Ensimmäinen toimitettu, joka täytti QC-kriteerit

Perjantai 3. maaliskuuta 2023

Ensimmäinen Lähetetty (Todellinen)

Tiistai 14. maaliskuuta 2023

Tutkimustietojen päivitykset

Viimeisin päivitys julkaistu (Todellinen)

Tiistai 29. syyskuuta 2026

Viimeisin lähetetty päivitys, joka täytti QC-kriteerit

Torstai 24. syyskuuta 2026

Viimeksi vahvistettu

Tiistai 1. syyskuuta 2026

Lisää tietoa

Tähän tutkimukseen liittyvät termit

Avainsanat

Muita asiaankuuluvia MeSH-ehtoja

Muut tutkimustunnusnumerot

  • AVENHIR
  • 2021-002007-35 (EudraCT-numero)
  • 2024-514878-53-00 (Ctis)

Yksittäisten osallistujien tietojen suunnitelma (IPD)

Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?

EI

Lääke- ja laitetiedot, tutkimusasiakirjat

Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta

Ei

Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta

Ei

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