Informations générales (source: ClinicalTrials.gov)
Phase II Study With Safety run-in of Azacitidine (AZA) Combined With Venetoclax (VEN) in Patients With Higher-risk Chronic Myelomonocytic Leukemia (CMML)
Interventional
Phase 2
Groupe Francophone des Myelodysplasies (Voir sur ClinicalTrials)
octobre 2023
octobre 2028
11 septembre 2025
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
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Christophe WILLEKENS | 05/06/2024 10:23:34 | Contacter | ||
| HOPITAL NOVO | BENRAMDANE Riad | 18/09/2025 17:50:04 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Avicenne | Thorsten BRAUN, MD/PhD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Cochin | Rudy BIRSEN, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Henri Becquerel - 76038 - Rouen - France | Aspasia STAMATOULLAS, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Annecy Genevois - Site d'Annecy - 74374 - Pringy - France | Adrien CONTEJEAN, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Mont de Marsan - 40000 - Mont-de-Marsan - France | Reza TABRIZI, MD | Contact (sur clinicalTrials) | |||
| Centre hospitalier Lyon sud - 69495 - Pierre-Bénite - France | Maël HEIBLIG, MD | Contact (sur clinicalTrials) | |||
| CHRU de Limoges - 87046 - Limoges - France | Marie-Pierre GOURIN, MD | Contact (sur clinicalTrials) | |||
| CHU d'Amiens - 80054 - Amiens - France | Delphine LEBON, MD | Contact (sur clinicalTrials) | |||
| CHU d'Angers - 49033 - Angers - France | Sylvain THEPOT, MD | Contact (sur clinicalTrials) | |||
| CHU de Bordeaux - Hôpital Haut-Lévêque - 33604 - Pessac - France | Sophie DIMICOLI-SALAZAR, MD | Contact (sur clinicalTrials) | |||
| CHU de Grenoble - 38043 - Grenoble - France | Sophie PARK, MD/PhD | Contact (sur clinicalTrials) | |||
| CHU de Montpellier - Hôpital Saint Eloi - 34295 - Montpellier - France | Franciane PAUL, MD | Contact (sur clinicalTrials) | |||
| CHU de Poitiers - 86021 - Poitiers - France | Jose Miguel TORREGROSA DIAZ, MD | Contact (sur clinicalTrials) | |||
| CHU de Tours - Hôpital Bretonneau - 37000 - Tours - France | Emmanuel GYAN, MD/PhD | Contact (sur clinicalTrials) | |||
| CHU Hôtel Dieu - 44093 - Nantes - France | Alice GARNIER, MD | Contact (sur clinicalTrials) | |||
| Hôpital Archet 1 - 06200 - Nice - France | Thomas CLUZEAU, MD/PhD | Contact (sur clinicalTrials) | |||
| Hôpital Claude Huriez - 59037 - Lille - France | Laure GOURSAUD, MD | Contact (sur clinicalTrials) | |||
| Hôpital Pontchaillou - 35033 - Rennes - France | Stanislas NIMUBONA, MD | Contact (sur clinicalTrials) | |||
| Hôpital privé du Confluent SAS - 44277 - Nantes - France | Jacques DELAUNAY, MD | Contact (sur clinicalTrials) | |||
| Hôpital privé Sévigné - 35510 - Cesson-Sévigné - France | Anne-Violaine DONCKER, MD | Contact (sur clinicalTrials) | |||
| Hôpital Saint Louis - 75010 - Paris - France | Raphaël ITZYKSON, MD/PhD | Contact (sur clinicalTrials) | |||
| IUCT oncopole - 31059 - Toulouse - France | Thibault COMONT, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
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.
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.