NCT05025423

Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

The proposed study is an open-label, single arm phase II study of venetoclax in combination with rituximab in patients over the age of 60 with previously untreated mantle cell lymphoma. The primary objective of the trial is to determine whether the combination of venetoclax with rituximab in this patient population yields a clinically acceptable proportion of overall responses (ORR, assessed by PET/CT with Lugano criteria) without chemotherapy.

Detailed description

For young, fit patients with mantle cell lymphoma, intensive chemotherapy and rituximab followed by ASCT is often used to achieve prolonged disease free survival. However, this therapy is not curative and has not been shown to improve overall survival. For older or frail patients, who are ineligible for stem cell transplantation, improved disease free survival can be achieved with chemotherapy and rituximab without ASCT, but at the cost of significant short and long-term toxicity. Venetoclax monotherapy has shown impressive single-agent activity in relapsed and refractory mantle cell lymphoma with low rates of adverse events. The hypothesis is that initial therapy with venetoclax and rituximab will result in rates of CR and PR that are comparable to historical rates with chemoimmunotherapy. Furthermore, this regimen will have fewer side effects than traditional therapy. Investigators also hypothesize that patients achieving a CR will have long durations of response that will continue after stopping venetoclax. Study investigators will test this hypothesis with an open label, single arm phase II trial with a target accrual of 40 participants. This study will include patients over age 60 who are not candidates for aggressive upfront therapy . Subjects will receive venetoclax and rituximab for up to 12 cycles of 4 weeks each. All patients will stop venetoclax after 12 cycles. Participants who have stable disease or disease progression after 4 cycles will be removed from the trial in order to receive standard of care chemoimmunotherapy. Participants who do not achieve a CR after 8 cycles of venetoclax and rituximab will receive 4 cycles of standard of care bendamustine in addition to continuing rituximab and venetoclax. This is the first phase II study of venetoclax and rituximab alone as initial therapy for mantle cell lymphoma. In the relapsed and refractory setting, venetoclax has shown high activity in MCL, and as such is a promising option for a non-chemotherapy approach to upfront treatment.

Conditions

• Mantle Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Venetoclax Oral Tablet [Venclexta]	Sequential dose levels for Venetoclax dependent on patient response. Fixed doses of 375 mg/m2 rituximab. Fixed dose of Bendamustine 90 mg/m2 added for those with continued PR at Cycle 8

Timeline

• Start date: 2022-06-21
• Primary completion: 2025-05-14
• Completion: 2025-05-14
• First posted: 2021-08-27
• Last updated: 2025-06-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study