Trial Title:
Oral Azacitidine Combined with Venetoclax in Previously Untreated Higher-risk Myelodysplastic Syndromes
NCT ID:
NCT05782127
Condition:
Untreated Myelodysplastic Syndrome
Conditions: Official terms:
Preleukemia
Myelodysplastic Syndromes
Syndrome
Venetoclax
Conditions: Keywords:
MDS
Oral Azacitidine
Venetoclax
Study type:
Interventional
Study phase:
Phase 1/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:
Onureg + Venetoclax
Description:
Combination of Onureg and Venetoclax
Arm group label:
Onureg + Venetoclax
Other name:
CC-486 + ABT-199
Summary:
This phase I/II open-label, dose-finding, multi-center study will assess safety and
primary efficacy of Onureg and Venetoclax combination, to define the optimal biological
dose and optimal treatment duration of Onureg to be used along with Venetoclax for
further studies in previously untreated patients with higher-risk myelodysplastic
syndromes (HR-MDS) not eligible to transplant.
Detailed description:
During phase I, three dose features of Onureg will be tested in combination with a fixed
dose of Venetoclax to define the optimal biological dose for phase II.
The phase II will assess safety and primary efficacy of Onureg and Venetoclax
combination, to define the optimal biological dose and optimal treatment duration of
Onureg to be used along with Venetoclax for further studies in previously untreated
patients with HR-MDS not eligible to transplant.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subjects must understand and voluntarily sign and date an ICF indicating the
investigational nature of the study, approved by an independent EC/IRB, prior to the
initiation of any screening or study-specific procedures.
2. Age ≥ 18 years at the date of signing the ICF.
3. Diagnosis of MDS according to the 2016 WHO classification (13) (Appendix 1), with
presence of < 20% bone marrow blasts per bone marrow aspirate at screening,
confirmed by local investigator with HR-MDS, based on the revised International
Prognostic Scoring System (IPSS-R) >3 (intermediate, high or very high) (14)
(Appendix 2) and a blast percentage of 5 or more.
4. Previously untreated HR-MDS: no prior therapy for MDS with any hypomethylating
agents (azacitidine or decitabine), chemotherapy, allo-Hematopoietic Stem Cell
Transplantation (HSCT) or experimental agent. All other treatments are not
considered prior therapy.
5. Not immediately eligible for allo-HSCT or intensive chemotherapy at the time of
screening due to individual clinical factors such as age, comorbidities and
performance status, donor availability.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
7. Total white blood cell (WBC) count ≤ 10 G/L; Treatment with hydroxyurea is permitted
to lower the WBC to reach this inclusion criterion and will be stopped at least 48
hours before treatment initiation.
8. Adequate liver functions as demonstrated by:
- Serum alanine transaminase (ALT) < 3.0 × upper limit of normal [ULN];
- Serum aspartate transaminase (AST) < 3.0 × ULN;
- Serum total bilirubin ≤ 2.0 × ULN (except in the setting of isolated Gilbert
syndrome, where participants may only be included with total bilirubin ≤ 3.0 x
ULN)
9. Adequate renal function with calculated creatinine clearance ≥ 40 mL/min/1.73 m²
(estimation based on Modification of Diet in Renal Disease (MDRD) formula or
CKD-EPI, by local laboratory).
10. Participant is able to communicate with the investigator, and has the ability to
comply with the requirements of the study procedures, available for regular blood
sampling, study related assessments, including bone marrow aspirates and appropriate
clinical management at the treating institution for the duration of the study.
11. Females of childbearing potential (FCBP) is a female who: 1) has achieved menarche
at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3)
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). FCBP must agree to
undergo medically supervised pregnancy test prior to starting study drug, during the
course of the study, and after end of study therapy:
- Have one negative pregnancy test as verified by the Investigator prior to
starting study therapy. The first pregnancy test will be performed at screening
(within 3 days prior to first study drug administration), and a negative
urinary test before starting all subsequent cycles. This applies even if the
participant practices true abstinence from heterosexual contact or agree to
use, and be able to comply with highly effective contraception without
interruption, 28 days prior to starting investigational product, during the
study therapy (including dose interruptions), and for 6 months after last dose
of Onureg, or at least 1 month after the last dose of venetoclax, whichever is
later or longer if required by local regulations.
- Female patients are either post-menopausal, free from menses for > 2 years,
surgically sterilized or willing to use 2 adequate barrier methods of
contraception to prevent pregnancy or agree to abstain from becoming pregnant
throughout the study, starting with Visit 1. Females of reproductive potential
as well as fertile men and their partners who are female of reproductive
potential must agree to abstain from sexual intercourse or to use two highly
effective forms of contraception from the time of giving informed consent,
during the study and for 6 months (females and males) following the last dose
of treatment.
12. Male participants must practice true abstinence (which must be reviewed on a monthly
basis) or agree to use an adequate method of contraception for the duration of the
study. Men should be advised not to father a child while receiving treatment and for
3 months post study. Men must agree to learn about the procedures for preservation
of sperm before starting treatment.
Exclusion Criteria:
1. Previous treatment for MDS, any approved or investigational antineoplastic agents or
radiotherapy.
2. Previous diagnosis of:
- MDS evolving from a pre-existing myeloproliferative neoplasm (MPN)
- MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic
myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and
unclassifiable MDS/MPN.
3. Participant has an active, uncontrolled systemic fungal, bacterial, or viral
infection. The participant should be afebrile and off antibiotics for at least 72
hours and off antifungals for 7 days. In the case of prior SARS-CoV-2 infection,
symptoms must have completely resolved and based on Investigator assessment in
consultation with the Medical Monitor, there are no sequelae that would place the
patient at a higher risk of receiving investigational treatment.
4. History of clinically significant medical conditions, laboratory abnormality,
psychiatric illness or any other reason that the investigator determines would
interfere with the subject's participation in this study, would make the subject an
unsuitable candidate to receive study drug or predisposes the participant to high
risk of noncompliance with the protocol.
5. History of active malignancy within the past year prior to screening, with the
exception of:
- Adequately treated carcinoma in situ of the uterine cervix
- Adequately treated basal cell carcinoma or localized squamous cell carcinoma of
the skin
- Asymptomatic prostate cancer without known metastatic disease and with no
requirement for therapy.
Patients with ongoing horomonotherapy could be included.
6. Participant has received strong or moderate CYP3A inhibitors or inducers or p-gp
inhibitors within 7 days prior to initiation of study treatment with prolonged
treatment required without therapeutic alternatives. Azols are the only exception
and may be permitted after cycle 1 at investigator's discretion and will result in
venetoclax dose reduction.
7. Consumption of grapefruit products, Seville oranges or starfruit within 3 days prior
to first dose of venetoclax.
8. Received live attenuated vaccines prior to initiation of study treatment.
9. History of clinically significant (per investigator's judgment) drug or alcohol
abuse within the last 6 months.
10. Conditions that could interfere with drug absorption including short gut syndrome,
dysphagia, gastroparesis, or other conditions that limit the ingestion or
gastrointestinal absorption of drugs administered orally.
11. Participant has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg
or diastolic BP > 100 mmHg) or has not been stable for at least 1 month prior to
treatment.
12. Significant active cardiac disease within the previous 6 months prior to signing the
ICF, including:
- New York Heart Association (NYHA) Class III or IV congestive heart failure
- Unstable angina or angina requiring surgical or medical intervention
- Significant cardiac arrhythmia
- And/or myocardial infarction
13. Participant is a pregnant or lactating female.
14. Participant has known or suspected to have hypersensitivity to any of the components
of the assigned study treatments.
15. Positive test result(s) for human immunodeficiency virus (HIV), hepatitis B virus
(HBV), or hepatitis C virus (HCV). Subjects with serologic evidence of prior
vaccination to hepatitis B virus (i.e., hepatitis B surface antigen [HBsAg]
negative, anti-hepatitis B surface [HBs] antibody positive and anti-hepatitis B core
[HBc] antibody negative) may participate.
16. Absence of social security affiliation.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU d'Amiens Picardie - Site sud
Address:
City:
Amiens
Zip:
80054
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Magalie JORIS, MD
Phone:
+33 3 22 45 54 66
Email:
joris.magalie@chu-amiens.fr
Contact backup:
Last name:
Magalie FOSSARD, MD
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
Contact backup:
Last name:
Sylvain THEPOT, MD
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
Contact backup:
Last name:
Thorsten BRAUN, MD/PhD
Facility:
Name:
CHU de Grenoble
Address:
City:
Grenoble
Zip:
38043
Country:
France
Status:
Recruiting
Contact:
Last name:
Sophie PARK, MD/PhD
Phone:
+33 4 76 76 62 77
Email:
spark@chu-grenoble.fr
Contact backup:
Last name:
Sophie PARK, MD/PhD
Facility:
Name:
CH Le Mans
Address:
City:
Le Mans
Zip:
72037
Country:
France
Status:
Recruiting
Contact:
Last name:
Kamel LARIBI, MD
Phone:
+33 2 43 43 43 61
Email:
klaribi@ch-lemans.fr
Contact backup:
Last name:
Kamel LARIBI, MD
Facility:
Name:
Hôpital Saint Vincent de Paul
Address:
City:
Lille
Zip:
59020
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laurent PASCAL, MD/PhD
Phone:
+33 3 20 87 45 32
Email:
pascal.laurent@ghicl.net
Contact backup:
Last name:
Laurent Laurent, MD/PhD
Facility:
Name:
CHU de Limoges - Hôpital Dupuytren
Address:
City:
Limoges
Zip:
87042
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
Contact backup:
Last name:
Marie-Pierre GOURIN, MD
Facility:
Name:
CH Lyon sud
Address:
City:
Lyon
Zip:
69495
Country:
France
Status:
Recruiting
Contact:
Last name:
Gaëlle FOSSARD, MD
Phone:
+33 4 78 86 22 69
Email:
gaelle.fossard@chu-lyon.fr
Contact backup:
Last name:
Gaëlle FOSSARD, MD
Facility:
Name:
Institut Paoli Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Colombe SAILLARD, MD
Phone:
+33 4 91 22 36 95
Email:
saillardc@ipc.unicancer.fr
Contact backup:
Last name:
Colombe SAILLARD, MD
Facility:
Name:
CHI 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
Contact backup:
Last name:
REZA TABRIZI, MD
Facility:
Name:
CHU 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
Contact backup:
Last name:
Franciane PAUL, MD
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
Contact backup:
Last name:
Alice GARNIER, MD
Facility:
Name:
Hôpital Archet 1
Address:
City:
Nice
Zip:
06200
Country:
France
Status:
Recruiting
Contact:
Last name:
Thomas CLUZEAU, MD/PhD
Phone:
+33 4 92 03 96 18
Email:
cluzeau.t@chu-nice.fr
Contact backup:
Last name:
Thomas CLUZEAU, MD/PhD
Facility:
Name:
CHU Nîmes - Institut de Cancérologie du Gard
Address:
City:
Nîmes
Zip:
30029 cedex 9
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Dr Stefan WICKENHAUSER, MD
Phone:
04 66 68 40 33
Email:
stefan.wickenhauser@chu-nimes.fr
Facility:
Name:
Hôpital Saint Louis
Address:
City:
Paris
Zip:
75010
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Pierre FENAUX, MD/PhD
Phone:
+33 1 71 20 70 22
Email:
pierre.fenaux@aphp.fr
Contact backup:
Last name:
Pierre FENAUX, MD/PhD
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
Contact backup:
Last name:
Rudy BIRSEN, MD
Facility:
Name:
CHU de Haut-Lévèque
Address:
City:
Pessac
Zip:
33604
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Sophie DIMICOLI-SALAZAR, MD
Phone:
+33 5 57 65 67 27
Email:
sophie.dimicoli-salazar@chu-bordeaux.fr
Contact backup:
Last name:
Sophie DIMICOLI-SALAZAR, MD
Facility:
Name:
CHU de Poitiers
Address:
City:
Poitiers
Zip:
86021
Country:
France
Status:
Recruiting
Contact:
Last name:
Jose Miguel TORREGROSA DIAZ, MD
Phone:
+33 5 48 44 44 44
Email:
jose-miguel.torregrosa-diaz@chu-poitiers.fr
Contact backup:
Last name:
Jose Miguel TORREGROSA DIAZ, MD
Facility:
Name:
Centre Henri Becquerel
Address:
City:
Rouen
Zip:
76038
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Aspasia STAMATOULLAS, MD
Phone:
+33 2 32 08 22 88
Email:
aspasia.stamatoullas@chb.unicancer.fr
Contact backup:
Last name:
Aspasia STAMATOULLAS, MD
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
Contact backup:
Last name:
Thibault COMONT, MD
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
Contact backup:
Last name:
Emmanuel GYAN, MD/PhD
Facility:
Name:
CH Valence
Address:
City:
Valence
Zip:
26000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Clémence SANTANA, MD
Phone:
+33 4 75 75 25 92
Email:
clemence.santana@ch-valence.fr
Contact backup:
Last name:
Clémence SANTANA, MD
Facility:
Name:
Hôpital Brabois
Address:
City:
Vandœuvre-lès-Nancy
Zip:
54500
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Maud D'AVENI-PINEY, MD
Phone:
+33 3 83 15 32 82
Email:
m.daveni-piney@chru-nancy.fr
Contact backup:
Last name:
Maud D'AVENI-PINEY, MD
Facility:
Name:
CH Annecy Genevois
Address:
City:
Épagny
Zip:
74370
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Adrien CONTEJEAN, MD
Phone:
+33 4 50 63 66 08
Email:
acontejean@ch-annecygenevois.fr
Contact backup:
Last name:
Adrien CONTEJEAN, MD
Start date:
December 6, 2023
Completion date:
November 2028
Lead sponsor:
Agency:
Groupe Francophone des Myelodysplasies
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
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/NCT05782127
