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)

NCT04790903 | Terminated Phase 1 FDA Drug

• 2 other identifiers: BO422032020-002376-12
• Study Type: interventional
• Target: 50
• Locations: 4 countries
• Sites: 20

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Dose-Limiting Toxicities (DLTs)

  Cycle 1 Day 1 up to but not including Cycle 3 Day 1 (Cycle length = 21 days)

Secondary Outcomes (7)

• Percentage of Participants with Adverse Events (AEs)

  Up to 4 years

• Complete Response (CR) rate at the end of treatment

  Up to 4 years

• Objective Response Rate (ORR) at the end of treatment

  Up to 4 years

• Duration of Response (DOR)

  Up to 4 years

• Progression-Free Survival (PFS)

  Up to 4 years

Study Arms (2)

Venetoclax (Schedule A)

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

Venetoclax (Schedule B)

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

Interventions

Venetoclax DRUG

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

Venetoclax (Schedule A); Venetoclax (Schedule B)

Polatuzumab Vedotin 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.

Venetoclax (Schedule A); Venetoclax (Schedule B)

Rituximab DRUG

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

Venetoclax (Schedule A); Venetoclax (Schedule B)

Cyclophosphamide 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.

Venetoclax (Schedule A); Venetoclax (Schedule B)

Doxorubicin 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.

Venetoclax (Schedule A); Venetoclax (Schedule B)

Prednisone DRUG

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

Venetoclax (Schedule A); Venetoclax (Schedule B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (20)

NYU Langone Hospitals, NYU Langone Rusk Ambulatory Surgical Pharmacy

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

SARAH CANNON RESEARCH INST.; Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

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

Lille, 59037, France

Location

CHU Montpellier - Saint ELOI

Montpellier, 34295, France

Location

CHU de Nantes; Cancéro-dermatologie

Nantes, 44093, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Centre Hospitalier Lyon Sud; Service d'Oncologie Médicale

Pierre-Bénite, 69310, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

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

Napoli, Campania, 80131, Italy

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

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

Meldola, Emilia-Romagna, 47014, Italy

Location

Ospedale Santa Maria Delle Croci

Ravenna, Emilia-Romagna, 48100, Italy

Location

Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia

Pisa, Piedmont, 56126, Italy

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

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

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario La Fe; Servicio de Farmacia

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

venetoclax; polatuzumab vedotin; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 10, 2021
• Study Start: July 2, 2021
• Primary Completion: May 21, 2024
• Study Completion: May 21, 2024
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7); IT (5); ES (5); US (3)