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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

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BO42203
  • SECONDARY ID: 2020-002376-12
  • NCT ID: NCT04790903

Conditions

  • Lymphoma, Large B-Cell, Diffuse

Interventions

DrugSynonymsArms
VenetoclaxVenetoclax (Schedule A)
Polatuzumab VedotinVenetoclax (Schedule A)
RituximabVenetoclax (Schedule A)
CyclophosphamideVenetoclax (Schedule A)
DoxorubicinVenetoclax (Schedule A)
PrednisoneVenetoclax (Schedule A)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Venetoclax (Schedule A)ExperimentalParticipants 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.
  • Venetoclax
  • Polatuzumab Vedotin
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone
Venetoclax (Schedule B)ExperimentalParticipants 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.
  • Venetoclax
  • Polatuzumab Vedotin
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame:Cycle 1 Day 1 up to but not including Cycle 3 Day 1 (Cycle length = 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with Adverse Events (AEs)
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Complete Response (CR) rate at the end of treatment
Time Frame:Up to 4 years
Safety Issue:
Description: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)
Measure:Objective Response Rate (ORR) at the end of treatment
Time Frame:Up to 4 years
Safety Issue:
Description: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
Measure:Duration of Response (DOR)
Time Frame:Up to 4 years
Safety Issue:
Description: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
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 4 years
Safety Issue:
Description: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
Measure:Plasma Concentrations of Venetoclax at specified timepoints
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Plasma Concentrations of Polatuzumab Vedotin analytes at specified timepoints
Time Frame:Up to 4 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

July 7, 2021