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)

Lymphoma, Large B-Cell, Diffuse Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04790903
• Other study ID #: BO42203
• Secondary ID: 2020-002376-12
• Status: Completed
• Phase: Phase 1
• Start date: July 2, 2021
• Est. completion date: May 21, 2024

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 21, 2024
• Est. primary completion date: May 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Venetoclax
Participants will self-administer Venetoclax, as described in the Arm Descriptions.
• 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 or bolus on Day 1 of Cycles 1-6.
• 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.
• Prednisone
Participants will receive Prednisone orally (PO) at a dose of 100 mg/day on Days 1-5 of Cycles 1-6.

Locations

Country	Name	City	State
France	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 Benite
France	CHU Rennes - Hopital Pontchaillou	Rennes cedex 09
France	Centre Henri Becquerel	Rouen
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	Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica	Napoli	Campania
Italy	Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia	Pisa	Piemonte
Italy	Ospedale Santa Maria Delle Croci	Ravenna	Emilia-Romagna
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	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario La Fe; Servicio de Farmacia	Valencia
United States	SARAH CANNON RESEARCH INST.; Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU Langone Hospitals, NYU Langone Rusk Ambulatory Surgical Pharmacy	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants with Adverse Events (AEs)		Up to 4 years
Secondary	Complete Response (CR) rate at the end of treatment	Assessed by the investigator on PET and computed tomography (PET/CT) scans according to the Lugano Response Criteria for Malignant Lymphoma (Cheson et al. 2014)	Up to 4 years
Secondary	Objective Response Rate (ORR) at the end of treatment	Defined as the proportion of patients with a CR or a partial response (PR), as determined by the investigator on PET/CT scans according to the Lugano 2014 Response Criteria	Up to 4 years
Secondary	Duration of Response (DOR)	Defined as the time from the first occurrence of a documented objective response (a PR or a CR) to disease progression, relapse, or death from any cause (whichever occurs first), as determined by the investigator according to the Lugano 2014 Response Criteria	Up to 4 years
Secondary	Progression-Free Survival (PFS)	Defined as the time from the date of first study treatment to the first occurrence of disease progression or relapse, as assessed by the investigator, according to the Lugano 2014 Response Criteria, or death from any cause, whichever occurs earlier	Up to 4 years
Secondary	Plasma Concentrations of Venetoclax at specified timepoints		Up to 4 years
Secondary	Plasma Concentrations of Polatuzumab Vedotin analytes at specified timepoints		Up to 4 years