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Azacitidin in Kombination mit Venetoclax bei Patienten mit chronischer myelomonozytärer Leukämie mit höherem Risiko (AVENHIR) (AVENHIR)

24. September 2026 aktualisiert von: Groupe Francophone des Myelodysplasies

Phase-II-Studie mit Sicherheits-Run-in von Azacitidin (AZA) in Kombination mit Venetoclax (VEN) bei Patienten mit chronischer myelomonozytärer Leukämie (CMML) mit höherem Risiko

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

Studienübersicht

Status

Aktiv, nicht rekrutierend

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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

Studientyp

Interventionell

Einschreibung (Geschätzt)

44

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Arzneimittel: Venetoclax

Combination of Azacitidine and Venetoclax

Andere Namen:
  • ABT-199

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Safety run-in
Zeitfenster: 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
Zeitfenster: 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)

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Complete remission rate
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Andere Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Patient reported outcomes
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Groupe Francophone des Myelodysplasies

Mitarbeiter

AbbVie

Ermittler

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

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

4. Oktober 2023

Primärer Abschluss (Tatsächlich)

16. Juni 2026

Studienabschluss (Geschätzt)

1. Oktober 2028

Studienanmeldedaten

Zuerst eingereicht

23. Februar 2023

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

3. März 2023

Zuerst gepostet (Tatsächlich)

14. März 2023

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

29. September 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

24. September 2026

Zuletzt verifiziert

1. September 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

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

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

NEIN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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