Trial Outcomes & Findings for Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age (NCT NCT03834688)

Last Updated: 2025-08-11

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

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

Results posted on

2025-08-11

Participant Flow

Participant milestones

Participant milestones
Measure	Induction Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Overall Study STARTED	33
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Induction n=33 Participants Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	30 Participants n=5 Participants
Age, Continuous	71 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	33 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	9 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	21 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	3 Participants n=5 Participants
Mantle Cell Lymphoma (MCL) International Prognostic Index (MIPI) Risk Category Low risk	2 Participants n=5 Participants
Mantle Cell Lymphoma (MCL) International Prognostic Index (MIPI) Risk Category Intermediate risk	9 Participants n=5 Participants
Mantle Cell Lymphoma (MCL) International Prognostic Index (MIPI) Risk Category High risk	22 Participants n=5 Participants

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	Induction n=33 Participants Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Complete Response (CR) Rate at End of Induction Complete response	28 Participants
Complete Response (CR) Rate at End of Induction Partial response	4 Participants
Complete Response (CR) Rate at End of Induction Stable disease	0 Participants
Complete Response (CR) Rate at End of Induction Progressive disease	0 Participants
Complete Response (CR) Rate at End of Induction Unevaluable	1 Participants

SECONDARY outcome

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

Number of participants with abnormal laboratory values and/or adverse events including Tumor Lysis Syndrome (TLS) were assessed using CTCAE v5.0. The adverse events were graded on a scale of 1 to 5 based on severity: grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life-threatening, and grade 5 resulted in death.

Outcome measures

Outcome measures
Measure	Induction n=33 Participants Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 Grade 1	5 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 Grade 2	8 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 Grade 3	11 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 Grade 4	6 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 Grade 5	2 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 No treatment-related AE	1 Participants

SECONDARY outcome

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

Objective response was assessed in accordance with the Lugano Classification Criteria using PET/CT scans (at baseline) and PET/CT or CT scans (during follow-up). Objective response is defined as the number of patients with a best treatment response of complete (CR) or partial response (PR).

Outcome measures

Outcome measures
Measure	Induction n=33 Participants Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Overall Response Complete or partial response	32 Participants
Overall Response Stable or progressive disease, or unevaluable	1 Participants

SECONDARY outcome

Timeframe: 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.

Progression-Free Survival (PFS) is a measure of patients that are alive and progression-free. Survival status is ascertained via direct contact and disease progression was assessed in accordance with the Lugano Classification Criteria using PET/CT scans (at baseline) and PET/CT or CT scans (during follow-up).

Outcome measures

Outcome measures
Measure	Induction n=33 Participants Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Progression-Free Survival (PFS)	59.0 Percentage of Participants Interval 33.7 to 77.5

SECONDARY outcome

Timeframe: 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.

Patients' survival status was measured by direct contact. The proportion of patients that are alive at the 4-year study timepoint is reported.

Outcome measures

Outcome measures
Measure	Induction n=33 Participants Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Overall Survival (OS)	61.3 Percentage of Participants Interval 36.2 to 79.0

Adverse Events

Induction

Serious events: 10 serious events

Other events: 19 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Induction n=33 participants at risk Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Infections and infestations COVID-19 pneumonia	9.1% 3/33 • Number of events 3 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Renal and urinary disorders Acute kidney injury	3.0% 1/33 • Number of events 1 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.0% 1/33 • Number of events 1 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Infections and infestations Clostridium difficile colitis	3.0% 1/33 • Number of events 1 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Gastrointestinal disorders Nausea/Vomiting	3.0% 1/33 • Number of events 1 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.0% 1/33 • Number of events 1 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Metabolism and nutrition disorders Tumour lysis syndrome	6.1% 2/33 • Number of events 2 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.

Other adverse events

Other adverse events
Measure	Induction n=33 participants at risk Venetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days. Venetoclax: 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). Bendamustine: 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. Rituximab: 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.
Blood and lymphatic system disorders Anaemia	6.1% 2/33 • Number of events 2 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Infections and infestations COVID-19 pneumonia	9.1% 3/33 • Number of events 3 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Investigations Lymphocyte count decreased	27.3% 9/33 • Number of events 12 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Investigations Neutropenia	24.2% 8/33 • Number of events 8 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Blood and lymphatic system disorders Thrombocytopenia	15.2% 5/33 • Number of events 6 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	6.1% 2/33 • Number of events 2 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.
Investigations White blood cell count decreased	12.1% 4/33 • Number of events 4 • Patients were followed for up to 48 months, which covers 6 months of induction treatment and 24 months of maintenance treatment.

Additional Information

Opeyemi Jegede, Statistician

Dana-Farber Cancer Institute

Phone: (617) 582-7613

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place