A Study Evaluating the Safety, Efficacy and Pharmacokinetics of Venetoclax in Combination With Polatuzumab Vedotin Plus Rituximab (R) and Cyclophosphamide, Doxorubicin, Prednisone (CHP) in Participants With Untreated BCL-2 Immunohistochemistry (IHC)-Positive Diffuse Large B-Cell Lymphoma (DLBCL)

NCT ID: NCT04790903

Last Updated: 2024-07-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-02
• Study Completion Date: 2024-05-21

Brief Summary

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.

Conditions

Lymphoma, Large B-Cell, Diffuse

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Participants will self-administer Venetoclax, as described in the Arm Descriptions.

Polatuzumab Vedotin

Intervention Type: DRUG

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

Intervention Type: DRUG

Participants will receive Rituximab at a dose of 375 mg/m\^2 by IV infusion on Day 1 of Cycles 1-6.

Cyclophosphamide

Intervention Type: DRUG

Participants will receive Cyclophosphamide at a dose of 750 mg/m\^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

Doxorubicin

Intervention Type: DRUG

Participants will receive Doxorubicin at a dose of 50 mg/m\^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

Prednisone

Intervention Type: DRUG

Participants will receive Prednisone orally (PO) at a dose of 100 mg/day on Days 1-5 of Cycles 1-6.

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Participants will self-administer Venetoclax, as described in the Arm Descriptions.

Polatuzumab Vedotin

Intervention Type: DRUG

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

Intervention Type: DRUG

Participants will receive Rituximab at a dose of 375 mg/m\^2 by IV infusion on Day 1 of Cycles 1-6.

Cyclophosphamide

Intervention Type: DRUG

Participants will receive Cyclophosphamide at a dose of 750 mg/m\^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

Doxorubicin

Intervention Type: DRUG

Participants will receive Doxorubicin at a dose of 50 mg/m\^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

Prednisone

Intervention Type: DRUG

Participants will receive Prednisone orally (PO) at a dose of 100 mg/day on Days 1-5 of Cycles 1-6.

Interventions

Venetoclax

Participants will self-administer Venetoclax, as described in the Arm Descriptions.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Rituximab

Participants will receive Rituximab at a dose of 375 mg/m\^2 by IV infusion on Day 1 of Cycles 1-6.

Intervention Type: DRUG

Cyclophosphamide

Participants will receive Cyclophosphamide at a dose of 750 mg/m\^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

Intervention Type: DRUG

Doxorubicin

Participants will receive Doxorubicin at a dose of 50 mg/m\^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

Intervention Type: DRUG

Prednisone

Participants will receive Prednisone orally (PO) at a dose of 100 mg/day on Days 1-5 of Cycles 1-6.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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 test 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

NYU Langone Hospitals, NYU Langone Rusk Ambulatory Surgical Pharmacy

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

SARAH CANNON RESEARCH INST.; Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez

Lille, , France

CHU Montpellier - Saint ELOI

Montpellier, , France

CHU de Nantes; Cancéro-dermatologie

Nantes, , France

Hôpital Saint-Louis

Paris, , France

Centre Hospitalier Lyon Sud; Service d'Oncologie Médicale

Pierre-Bénite, , France

CHU Rennes - Hopital Pontchaillou

Rennes, , France

Centre Henri Becquerel

Rouen, , France

Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica

Napoli, Campania, Italy

Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; Dip. Scienze Mediche e Chirurgiche

Bologna, Emilia-Romagna, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST; Farmacia Oncologica

Meldola, Emilia-Romagna, Italy

Ospedale Santa Maria Delle Croci

Ravenna, Emilia-Romagna, Italy

Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia

Pisa, Piedmont, Italy

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital de la Santa Creu i Sant Pau; Servicio de Dermatologia

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital General Univ. Gregorio Maranon

Madrid, , Spain

Hospital Universitario La Fe; Servicio de Farmacia

Valencia, , Spain

Countries

United States; France; Italy; Spain

Other Identifiers

2020-002376-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO42203

Identifier Type: -

Identifier Source: org_study_id