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Azacytydyna w skojarzeniu z wenetoklaksem u pacjentów z przewlekłą białaczką mielomonocytową wysokiego ryzyka (AVENHIR) (AVENHIR)

24 września 2026 zaktualizowane przez: Groupe Francophone des Myelodysplasies

Badanie fazy II z bezpiecznym wprowadzeniem azacytydyny (AZA) w skojarzeniu z wenetoklaksem (VEN) u pacjentów z przewlekłą białaczką mielomonocytową (CMML) wysokiego ryzyka

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

Przegląd badań

Status

Aktywny, nie rekrutujący

Warunki

Interwencja / Leczenie

Szczegółowy opis

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

Typ studiów

Interwencyjne

Zapisy (Szacowany)

44

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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.
Lek: Venetoclax

Combination of Azacitidine and Venetoclax

Inne nazwy:
  • ABT-199

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Safety run-in
Ramy czasowe: 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
Ramy czasowe: 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)

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Complete remission rate
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Inne miary wyników

Miara wyniku
Opis środka
Ramy czasowe
Patient reported outcomes
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Groupe Francophone des Myelodysplasies

Współpracownicy

AbbVie

Śledczy

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

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

4 października 2023

Zakończenie podstawowe (Rzeczywisty)

16 czerwca 2026

Ukończenie studiów (Szacowany)

1 października 2028

Daty rejestracji na studia

Pierwszy przesłany

23 lutego 2023

Pierwszy przesłany, który spełnia kryteria kontroli jakości

3 marca 2023

Pierwszy wysłany (Rzeczywisty)

14 marca 2023

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

29 września 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

24 września 2026

Ostatnia weryfikacja

1 września 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

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

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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