Trouver des essais cliniques
Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.
Code de protocole Servier:
CL1-64315-002
Sponsor:
Institut de Recherches Internationales Servier
Identifiant Clinicaltrials.gov:
NCT03672695
Numéro EudraCT:
2018-001809-88
Trouver un site de recrutement
Comment participer à cette étude
Si vous pensez être éligible pour cette étude (voir
ci-dessous), vous pouvez identifier le site le plus proche de chez vous et le contacter directement. Si vous ne trouvez pas de site près de chez vous, veuillez contacter l'Institut de Recherches Internationales Servier (I.R.I.S.).
critères d'éligibilité
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Ceux-ci comprennent les critères d'inclusion et les critères d'exclusion. Parmi ces critères, on peut citer l'état de santé général d'une personne ou les traitements antérieurs qu'elle a suivis.
Nom:
Institut de Recherches Internationales Servier, Département des études cliniques
Numéro de téléphone:
+33 1 55 72 60 00
L'étude a 7 centres
Description de l'étude
The purpose of this study is to determine the safety profile, tolerability and the Recommended Phase 2 Dose of the combination S64315 with venetoclax in patients with Acute Myeloid Leukaemia.
Titre officiel: An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia (AML).
Indications
Acute Myeloid Leukaemia
Interventions / Traitements
Le ou les traitements administrés aux participants à l'étude.
- S 64315 (also referred as MIK665) and venetoclax
Autres numéros d'identification
Autres numéros d'identification sous lesquels l'étude peut être connue.
- CL1-64315-002
Critères d'éligibilité
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Ceux-ci comprennent les critères d'inclusion et les critères d'exclusion. Parmi ces critères, on peut citer l'état de santé général d'une personne ou les traitements antérieurs qu'elle a suivis.
Age éligible pour l’étude
18 ans et plus
(Adulte, Adulte plus âgé)
Sexe
Homme/FemmeAccepte les volontaires en bonne santé
Non- 1. Male or female aged ≥ 18 years;
- 2. Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization (WHO) 2016 classification (Arber, 2016), excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):
- * With relapsed or refractory disease without established alternative therapy or
- * Secondary to MDS treated at least by hypomethylating agent and without established alternative therapy or
- * ≥ 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative therapy
- 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- 4. Able to comply with study procedures
- 5. Adequate renal function within 7 days before the inclusion of the patient defined as:
- • Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2
- 6. Adequate hepatic function within 7 days before the inclusion of the patient defined as:
- * AST and ALT ≤ 1.5 x ULN
- * Total serum bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
- 1. Participant already enrolled and treated in the study
- 2. Pregnancy, breastfeeding or possibility of becoming pregnant during the study
- 3. Participation in another interventional study requiring investigational treatment intake at the same time or within 2 weeks or at least 5 halflives (whichever is longer) prior to first dose of IMP (participation in non-interventional registries or epidemiological studies is allowed). In case of biologic agents with a long half life such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat wash-out of 28 days will be acceptable
- 4. Presence of ≥ CTCAE Grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE, version 4.03).
- 5. Known carriers of HIV antibodies
- 6. Known history of significant liver disease
- 7. Uncontrolled hepatitis B or C infection
- 8. Known active acute or chronic pancreatitis
- 9. History of myocardial infarction (MI), unstable angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
- 10. Any factors that could increase the risk of QTc prolongation or risk of arrhythmic events.
Comment l'étude est-elle conçue ?
Allocation
Comment les participants sont répartis dans différents groupes. La répartition peut être aléatoire (randomisée) ou prédéterminée (non randomisée). Randomisée signifie que les participants sont répartis de manière aléatoire dans leur groupe/branche.
Modèle d'étude interventionnelle
Comment les traitements sont administrés et testés dans le cadre d'une étude.
Séquentiel
Une étude séquentielle consiste à tester des traitements les uns après les autres dans un ordre précis. Les chercheurs commencent par un traitement et, en fonction des résultats, décident de passer ou non au traitement suivant. Cette approche permet de comprendre les effets des traitements au fil du temps.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Initial Schedule - S64315 low dose and venetoclax high dose administered in combination
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Initial Schedule - S64315 medium dose and venetoclax low dose administered in combination
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Initial Schedule - S64315 medium dose and venetoclax medium dose administered in combination
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Initial Schedule - S64315 medium dose and venetoclax high dose administered in combination
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Initial Schedule - S64315 high dose and venetoclax medium dose administered in combination
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Alternative Schedule - Venetoclax medium dose administered with no S64315
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Alternative Schedule - S64315 medium dose and venetoclax medium dose administered in combination
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Groupe de participants / Bras de traitement
Un groupe de participants à l'étude qui reçoivent le même traitement ou la même intervention.
Expérimental:
Alternative Schedule - S64315 high dose and venetoclax low dose administered in combination
Intervention / Traitement
Le ou les traitements administrés aux participants à l'étude.
Produit combiné:
S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Mots clés
Autres termes
Leukemia, Myeloid, Acute