Clinical trial NCT04790903: 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)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma, Large B-Cell, Diffuse
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-03-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 Day 1 up to but not including Cycle 3 Day 1 (Cycle length = 21 days)
Secondary outcomes:
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 4 years
measure: Complete Response (CR) rate at the end of treatment
timeFrame: Up to 4 years
measure: Objective Response Rate (ORR) at the end of treatment
timeFrame: Up to 4 years
measure: Duration of Response (DOR)
timeFrame: Up to 4 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 4 years
measure: Plasma Concentrations of Venetoclax at specified timepoints
timeFrame: Up to 4 years
measure: Plasma Concentrations of Polatuzumab Vedotin analytes at specified timepoints
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Hospitals, NYU Langone Rusk Ambulatory Surgical Pharmacy
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: SARAH CANNON RESEARCH INST.; Tennessee Oncology, PLLC
state: Tennessee
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
city: Montpellier
country: France
facility: CHU Montpellier - Saint ELOI
city: Nantes
country: France
facility: CHU de Nantes; Cancéro-dermatologie
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud; Service d'Oncologie Médicale
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; Dip. Scienze Mediche e Chirurgiche
state: Emilia-Romagna
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST; Farmacia Oncologica
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: Ospedale Santa Maria Delle Croci
state: Emilia-Romagna
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia
state: Piemonte
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Dermatologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Univ. Gregorio Maranon
city: Valencia
country: Spain
facility: Hospital Universitario La Fe; Servicio de Farmacia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: