Etude : BO42203 /



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : BO42203

Situation thérapeutique : Induction

Traitement : Chimiothérapie / Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 25/06/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Une étude de phase Ib évaluant l'innocuité, l'efficacité et la pharmacocinétique du vénétoclax en association avec le Polatuzumab Vedotin Plus Rituximab (R) et le cyclophosphamide, la doxorubicine, la prednisone (CHP) chez des patients atteints d'immunohistochimie BCL-2 non traitée Lymphome cellulaire.

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C83 - Lymphome non folliculaire
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This Phase Ib, open-label, multicenter study evaluates the safety, efficacy, and pharmacokinetics of venetoclax in combination with Pola + R-CHP in previously untreated participants with BCL-2 IHC-positive DLBCL. Approximately 50 participants will be enrolled in this study in five consecutive cohorts each consisting of approximately 10 participants.

STUDY ARMS:
- Experimental: Venetoclax (Schedule A)
Participants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below:
* Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows:
* Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.

- Experimental: Venetoclax (Schedule B)
Participants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below:
* Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows:
* Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.

Polatuzumab Vedotin: Participants will receive Polatuzumab Vedotin at a dose of 1.8 mg/kg by intravenous (IV) infusion on Day 1 of Cycles 1-6.
Rituximab: Participants will receive Rituximab at a dose of 375 mg/m^2 by IV infusion on Day 1 of Cycles 1-6.
Cyclophosphamide: Participants will receive Cyclophosphamide at a dose of 750 mg/m^2 by IV infusion on Day 1 of Cycles 1-6.
Doxorubicin: Participants will receive Doxorubicin at a dose of 50 mg/m^2 by IV infusion on Day 1 of Cycles 1-6.
Prednisone: Participants will receive Prednisone orally (PO) at a dose of 100 mg/day on Days 1-5 of Cycles 1-6.

CURRENT PRIMARY OUTCOME:
Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 Day 1 up to but not including Cycle 3 Day 1 (Cycle length = 21 days) ]

CURRENT SECONDARY OUTCOMES:
- Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 4 years ]
- Complete Response (CR) rate at the end of treatment [ Time Frame: Up to 4 years ]
- Objective Response Rate (ORR) at the end of treatment [ Time Frame: Up to 4 years ]
- Duration of Response (DOR) [ Time Frame: Up to 4 years ]
- Progression-Free Survival (PFS) [ Time Frame: Up to 4 years ]
- Plasma Concentrations of Venetoclax at specified timepoints [ Time Frame: Up to 4 years ]
- Plasma Concentrations of Polatuzumab Vedotin analytes at specified timepoints [ Time Frame: Up to 4 years ]

Phase : Ib

Stade : NA

1 (hémato)
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Previously untreated participants with CD20-positive DLBCL.
- BCL-2 protein overexpression by IHC, as assessed by local testing.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- International Prognostic Index (IPI) 2-5.
- Life expectancy of more than 6 months.
- Left ventricular ejection fraction (LVEF) ≥ 50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO).
- Availability of archival or freshly collected tumor tissue prior to study enrollment.
- At least one bi-dimensionally fluorodeoxyglucose-avid measurable lymphoma lesion on PET/CT scan, defined as > 1.5 cm in its longest dimension on CT scan.
- Adequate hematopoietic function.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.

Critères de non-inclusion : - Current diagnosis of unclassifiable B-cell lymphoma.
- Prior treatment for indolent lymphoma.
- Current Grade > 1 peripheral neuropathy.
- Prior organ transplantation.
- Prior use of any monoclonal antibody within 3 months and any investigational therapy within 28 days prior to the start of Cycle 1.
- Vaccination with live vaccines within 28 days prior to the start of Cycle 1.
- Prior therapy for DLBCL and High-Grade B-cell Lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids.
- Recent major surgery (within 6 weeks prior to the start of Day 1 of Cycle 1), other than for diagnosis.
- History of other cancers within 2 years prior to screening.
- Any active infection that, in the opinion of the investigator, would impact participant safety within 7 days prior to Day 1 of Cycle 1.
- Serious infection requiring oral or IV antibiotics within 4 weeks prior to Day 1 of Cycle 1.
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
- Positive for Hepatitis B/C Viruses (HBV/HCV) and Human T-cell Leukemia Virus (HTLV)-1.
- Known infection with HIV.
- History of progressive multifocal leukoencephalopathy.
- Suspected active or latent tuberculosis.
- Clinically significant history of liver disease, including viral or other hepatitis or cirrhosis.
- Substance abuse, including non-prescription drug and alcohol dependence, within 12 months prior to screening.
- Pregnant or breastfeeding, or intending to become pregnant during the study within 6 months after the final dose of venetoclax, 9 months after the final dose of polatuzumab vedotin, or 12 months after the final dose of rituximab.
- History or presence of an abnormal ECG that is clinically significant in the investigator's opinion.
- Malabsorption syndrome or other condition that would interfere with enteral absorption.
- Blood transfusion within 14 days prior to screening.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04790903
Promoteur :
HOFFMANN-LA ROCHE
Type de sponsor : Industriel
00000 HORS FRANCE

Coordonnateur :
Hoffmann-La Roche
global-roche-genentech-trials@gene.com
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Henri Becquerel - Rue d'Amiens CS 11516 - Cedex 1 - 76000 ROUEN

Investigateur :
Pr h. TILLY

TEC / ARC / IDE :
Justine LORET
justine.loret@
chb.unicancer.fr
02.32.08.30.45

Statut de l'essai : OUVERT

MAJ : 25/06/2021