Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age

NCT03834688 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: PrE0405ML40551
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 7

Brief Summary

Eligible untreated patients will receive single arm venetoclax, bendamustine and rituximab as induction therapy. After 6 cycles, maintenance rituximab may be administered per physician discretion. Venetoclax is an oral Bcl-2 family protein inhibitor. It targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with mantle cell lymphoma. Venetoclax may make the cancer cells sensitive to chemotherapy. This may help to slow down the growth of cancer or may cause cancer cells to die. The purpose of this study is to see if venetoclax in combination with bendamustine and rituximab chemotherapy is effective in treating people who have mantle cell lymphoma and to examine the side effects, good and bad, associated with this combination.

Conditions

Mantle Cell Lymphoma

Keywords

Venetoclax; Bendamustine; Rituximab; Bcl-2 Family Protein Inhibitor

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate at End of Induction

  Complete Response (CR) was assessed in accordance with the Lugano Classification Criteria using PET/CT scans (at baseline) and PET/CT or CT scans (during follow-up). Based on this criteria, a Deauville score ≤ 3 corresponds to a CR, a score of 4 or 5 and ≥ 50% decrease in the sum of lesion measurements corresponds to a Partial Response (PR), a score of 4 or 5 and \<50% decrease in sum of lesion measurements corresponds to a Stable Disease (SD), a score of 4 or 5 and \>1.5cm increase in a single lesion or presence of new lesions or bone marrow recurrence denotes Progressive Disease (PD).

  Complete Response (CR) status was assessed after 6 months of induction treatment, plus an additional 2 months for end of treatment PET/CT scans.

Secondary Outcomes (4)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0

  Adverse events were reported throughout 6 months of induction treatment and up to 2 months following completion of induction treatment

• Overall Response

  Objective response was assessed after 6 months of induction treatment, plus an additional 2 months for end of treatment PET/CT scans.

• Progression-Free Survival (PFS)

  Progression-Free Survival (PFS) was assessed from the start to completion of induction treatment (6 months) through the completion of maintenance treatment (24 months) for up to 48 months. PFS at the 4-year timepoint was estimated and reported.

• Overall Survival (OS)

  Overall survival (OS) was assessed from the start to completion of induction treatment (6 months) through the completion of maintenance treatment (24 months) for up to 48 months. OS at the 4-year timepoint was estimated and reported.

Study Arms (1)

Induction

EXPERIMENTAL

Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days.

Drug: Venetoclax; Drug: Bendamustine; Drug: Rituximab

Interventions

Venetoclax DRUG

Cycle 1: Venetoclax by mouth daily. The dose will gradually increase during Cycle 1. (Day 1-7: 20 mg; Day 8-14: 50 mg; Day 15-21: 100 mg; Day 22-28: 200 mg.) Cycles 2-6: Venetoclax 400 mg by mouth daily on Days 1-10 (1 cycle = 28 days).

Also known as: GDC-0199, ABT-199, RO5537382

Induction

Bendamustine DRUG

Cycle 1-6: Bendamustine 90 mg/m² intravenous (IV) on Days 1 and 2 of each cycle. Bendamustine may be started at 70 mg/m² in patients over the age of 75 years with comorbid conditions or patients over the age of 80 years without comorbid conditions.

Also known as: Bendamustine hydrochloride

Induction

Rituximab DRUG

Cycle 1-6: Rituximab 375 mg/m² IV on Day 1 of each cycle. After 2 consecutive cycles of Rituximab IV are well tolerated, Rituximab may be given subcutaneously.

Also known as: Chimeric anti-CD20 monoclonal antibody, Rituxan

Induction

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed (biopsy-proven) diagnosis of mantle cell lymphoma (MCL), with documented cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or Fluorescence In Situ Hybridization (FISH).
• Patients must have measurable or evaluable disease as defined as a lymph node measuring \>1.5 cm in any dimension or splenomegaly with spleen \>15 cm in craniocaudal dimension.
• Age ≥ 60 years.
• No intention to undergo consolidation with high dose chemotherapy and autologous stem cell rescue (Autologous Stem Cell Transplant) in first remission.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Ability to understand and willingness to sign Institutional Review Board (IRB)-approved informed consent.
• Willing to provide mandatory tissue samples (if sufficient tissue available), bone marrow and blood samples for research purposes.
• Adequate organ function as measured by the following criteria, obtained ≤ 2 weeks prior to registration:
• Absolute Neutrophil Count (ANC) ≥ 1000/mm³
• Hemoglobin ≥ 8 g/dL
• Platelets ˃75,000/mm³
• Creatinine clearance ≥ 40 mL/min, calculated with the use of 24-hour creatinine clearance or by Cockcroft-Gault formula
• Total Bilirubin ≤ 1.5x Upper Limit of Normal (ULN) or ≤ 3x ULN for patients with documented Gilbert's syndrome
• Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5x ULN
• All females of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a blood test to rule out pregnancy within 2 weeks prior to registration.

Sponsors & Collaborators

• PrECOG, LLC.: lead
• Genentech, Inc.: collaborator

Study Sites (7)

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

St. Joseph Mercy Hospital Cancer Care Center

Ann Arbor, Michigan, 48106, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

venetoclax; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

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)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Opeyemi Jegede, Statistician
• Organization: Dana-Farber Cancer Institute

ojegede@ds.dfci.harvard.edu

(617) 582-7613

Study Officials

• Craig Portell, MD

  University of Virginia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-Label, Single-Arm Study, Cycle 1 Dose Escalation

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 8, 2019
• Study Start: January 13, 2020
• Primary Completion: October 20, 2022
• Study Completion: July 26, 2024
• Last Updated: August 11, 2025
• Results First Posted: January 23, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)