Trial Title:
Azacitidine Combined With Venetoclax in Patients With Higher-risk Chronic Myelomonocytic Leukemia (AVENHIR)
NCT ID:
NCT05768711
Condition:
Chronic Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Venetoclax
Conditions: Keywords:
CMML
Azacitidine
Venetoclax
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Combination of Azacitidine and Venetoclax
Arm group label:
Azacidine+Venetoclax
Other name:
ABT-199
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
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
newly diagnosed, hypomethylating agent-naïve, higher-risk chronic myelomonocytic leukemia
patients
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age 18 and older.
2. CMML diagnosis according to WHO 2016 criteria.
3. Intermediate-2 or high risk according to the CMML Prognostic Scoring System (CPSS)
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. In patients with
failed or missing cytogenetics at screening, cytogenetics at CMML diagnosis will be
used to compute CPSS.
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) for < 6 weeks is acceptable. No washout is necessary
for those patients but pre-HY WBC will be taken in consideration for CPSS
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 at inclusion (WBC prior to HY used to compute CPSS at inclusion in
HY-exposed patients) or with a CPSS 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU d'Amiens
Address:
City:
Amiens
Zip:
80054
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Delphine LEBON, MD
Phone:
+33 3 22 45 59 14
Email:
lebon.delphine@chu-amiens.fr
Investigator:
Last name:
Delphine LEBON, MD
Email:
Principal Investigator
Facility:
Name:
CHU d'Angers
Address:
City:
Angers
Zip:
49033
Country:
France
Status:
Recruiting
Contact:
Last name:
Sylvain THEPOT, MD
Phone:
+33 2 41 35 44 75
Email:
sylvain.thepot@chu-angers.fr
Investigator:
Last name:
Sylvain THEPOT, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Avicenne
Address:
City:
Bobigny
Zip:
93009
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Thorsten BRAUN, MD/PhD
Phone:
+33 1 48 95 70 72
Email:
thorsten.braun@aphp.fr
Investigator:
Last name:
Thorsten BRAUN, MD/PhD
Email:
Principal Investigator
Facility:
Name:
Hôpital privé Sévigné
Address:
City:
Cesson-Sévigné
Zip:
35510
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Anne-Violaine DONCKER, MD
Phone:
+33 2 23 21 05 50
Email:
violainedoncker@gmail.com
Investigator:
Last name:
Anne-Violaine DONCKER, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Grenoble
Address:
City:
Grenoble
Zip:
38043
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Sophie PARK, MD/PhD
Phone:
+33 4 76 76 62 77
Email:
spark@chu-grenoble.fr
Investigator:
Last name:
Sophie PARK, MD/PhD
Email:
Principal Investigator
Facility:
Name:
CHRU de Limoges
Address:
City:
Limoges
Zip:
87046
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Marie-Pierre GOURIN, MD
Phone:
+33 5 55 05 66 42
Email:
marie-pierre.gourin@chu-limoges.fr
Investigator:
Last name:
Marie-Pierre GOURIN, MD
Email:
Principal Investigator
Facility:
Name:
Institut Paoli Calmettes
Address:
City:
Marseille
Zip:
13273
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Norbert VEY, MD/PhD
Phone:
+33 4 91 22 36 95
Email:
veyn@ipc.unicancer.fr
Investigator:
Last name:
Norbert VEY, MD/PhD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier de Mont de Marsan
Address:
City:
Mont-de-Marsan
Zip:
40000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Reza TABRIZI, MD
Phone:
+33 5 58 05 11 62
Email:
reza.tabrizi@ch-mdm.fr
Investigator:
Last name:
Reza TABRIZI, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Montpellier - Hôpital Saint Eloi
Address:
City:
Montpellier
Zip:
34295
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Franciane PAUL, MD
Phone:
+33 4 67 33 22 54
Email:
f-paul@chu-montpellier.fr
Investigator:
Last name:
Franciane PAUL, MD
Email:
Principal Investigator
Facility:
Name:
CHU Hôtel Dieu
Address:
City:
Nantes
Zip:
44093
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Alice GARNIER, MD
Phone:
+33 2 40 08 32 71
Email:
alice.garnier@chu-nantes.fr
Investigator:
Last name:
Alice GARNIER, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital privé du Confluent SAS
Address:
City:
Nantes
Zip:
44277
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Jacques DELAUNAY, MD
Phone:
+33 2 28 27 21 16
Email:
Jacques.delaunay@groupeconfluent.fr
Investigator:
Last name:
Jacques DELAUNAY, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Archet 1
Address:
City:
Nice
Zip:
06200
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Thomas CLUZEAU, MD/PhD
Phone:
+33 4 92 03 58 39
Email:
cluzeau.t@chu-nice.fr
Investigator:
Last name:
Thomas CLUZEAU, MD/PhD
Email:
Principal Investigator
Facility:
Name:
Hôpital Saint Louis
Address:
City:
Paris
Zip:
75010
Country:
France
Status:
Recruiting
Contact:
Last name:
Raphaël ITZYKSON, MD/PhD
Phone:
+33 1 42 38 51 27
Email:
raphael.itzykson@aphp.fr
Investigator:
Last name:
Raphaël ITZYKSON, MD/PhD
Email:
Principal Investigator
Facility:
Name:
Hôpital Cochin
Address:
City:
Paris
Zip:
75014
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Rudy BIRSEN, MD
Phone:
+33 1 58 41 21 20
Email:
rudy.birsen@aphp.fr
Investigator:
Last name:
Rudy BIRSEN, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Bordeaux - Hôpital Haut-Lévêque
Address:
City:
Pessac
Zip:
33604
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Sophie DIMICOLI-SALAZAR, MD
Phone:
+33 5 57 65 65 11
Email:
sophie.dimicoli-salazar@chubordeaux.fr
Investigator:
Last name:
Sophie DIMICOLI-SALAZAR, MD
Email:
Principal Investigator
Facility:
Name:
Centre hospitalier Lyon sud
Address:
City:
Pierre-Bénite
Zip:
69495
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Maël HEIBLIG, MD
Phone:
+33 4 78 86 22 34
Email:
mael.heiblig@chu-lyon.fr
Investigator:
Last name:
Maël HEIBLIG, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Poitiers
Address:
City:
Poitiers
Zip:
86021
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Jose Miguel TORREGROSA DIAZ, MD
Phone:
+33 5 48 44 44 44
Email:
jose-miguel.torregrosa-diaz@chu-poitiers.fr
Investigator:
Last name:
Jose Miguel TORREGROSA DIAZ, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier Annecy Genevois - Site d'Annecy
Address:
City:
Pringy
Zip:
74374
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Natacha MAUZ, MD
Phone:
+33 4 50 63 77 59
Email:
nmauz@ch-annecygenevois.fr
Investigator:
Last name:
Natacha MAUZ, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Pontchaillou
Address:
City:
Rennes
Zip:
35033
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Stanislas NIMUBONA, MD
Phone:
+33 2 99 28 95 21
Email:
stanislas.nimubona@chu-rennes.fr
Investigator:
Last name:
Stanislas NIMUBONA, MD
Email:
Principal Investigator
Facility:
Name:
Centre Henri Becquerel
Address:
City:
Rouen
Zip:
76038
Country:
France
Status:
Recruiting
Contact:
Last name:
Aspasia STAMATOULLAS, MD
Phone:
+33 2 32 08 22 88
Email:
aspasia.stamatoullas@chb.unicancer.fr
Investigator:
Last name:
Aspasia STAMATOULLAS, MD
Email:
Principal Investigator
Facility:
Name:
IUCT oncopole
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Recruiting
Contact:
Last name:
Thibault COMONT, MD
Phone:
+33 5 31 15 62 66
Email:
comont.thibault@iuct-oncopole.fr
Investigator:
Last name:
Thibault COMONT, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Tours - Hôpital Bretonneau
Address:
City:
Tours
Zip:
37000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Emmanuel GYAN, MD/PhD
Phone:
+33 2 47 25 87 78
Email:
emmanuel.gyan@univ-tours.fr
Investigator:
Last name:
Emmanuel GYAN, MD/PhD
Email:
Principal Investigator
Facility:
Name:
Institut Gustave Roussy
Address:
City:
Villejuif
Zip:
94800
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Christophe WILLEKENS, MD
Phone:
+33 1 42 11 23 79
Email:
christophe.willekens@gustaveroussy.fr
Investigator:
Last name:
Christophe WILLEKENS, MD
Email:
Principal Investigator
Start date:
October 4, 2023
Completion date:
October 2028
Lead sponsor:
Agency:
Groupe Francophone des Myelodysplasies
Agency class:
Other
Collaborator:
Agency:
AbbVie
Agency class:
Industry
Source:
Groupe Francophone des Myelodysplasies
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05768711
