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)
Status and phase
Terminated
Phase 1
Conditions
Lymphoma, Large B-Cell, Diffuse
Treatments
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Venetoclax
Drug: Prednisone
Drug: Rituximab
Drug: Polatuzumab Vedotin
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
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.
Enrollment
50 patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
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.
Trial design
Primary purpose
Treatment
Allocation
Non-Randomized
Interventional model
Sequential Assignment
Masking
None (Open label)
50 participants in 2 patient groups
Venetoclax (Schedule A)
Experimental group
Description:
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.
Treatment:
Drug: Rituximab
Drug: Polatuzumab Vedotin
Drug: Prednisone
Drug: Venetoclax
Drug: Doxorubicin
Drug: Cyclophosphamide
Venetoclax (Schedule B)
Experimental group
Description:
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.
Treatment:
Drug: Rituximab
Drug: Polatuzumab Vedotin
Drug: Prednisone
Drug: Venetoclax
Drug: Doxorubicin
Drug: Cyclophosphamide
Trial contacts and locations
20
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Central trial contact
Reference Study ID Number: BO42203 https://forpatients.roche.com/
Data sourced from clinicaltrials.gov
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