NCT03609593

Bendamustine/Rituximab Followed by Venetoclax and Rituximab for Treatment of Chronic Lymphocytic Leukemia

A Single-arm, Multi-center Phase II Trial of Bendamustine/Rituximab Induction Followed by Venetoclax and Rituximab Consolidation for the Frontline Treatment of Chronic Lymphocytic Leukemia (CLL)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (actual)
• Sponsor: Nicole Lamanna · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 months. Bendamustine and rituximab is a commonly used treatment for CLL. Venetoclax is an oral drug that blocks a protein called BCL-2 which is present on CLL cells. It is approved for patients with relapsed (the cancer has come back) or refractory (the cancer did not respond) CLL who harbor a deletion in the short arm of chromosome 17 \[del(17p)\]. When this drug is used by itself, many patients needed to be admitted to the hospital to monitor for a complication known as tumor lysis syndrome. This is an oncologic emergency that is caused by massive destruction of tumor cells with the release of large amounts of electrolytes and other molecules into the blood that can lead to renal failure and potentially death.

Detailed description

This is a single arm multicenter phase II study using bendamustine-rituximab (BR) followed by venetoclax and rituximab for the upfront treatment of chronic lymphocytic leukemia (CLL). The activity, safety, and survival data have been presented previously for BR alone in patients with previously untreated disease and venetoclax alone in relapsed/refractory patients and those with high-risk disease. After pretreatment evaluation, patients will receive three cycles of BR followed by venetoclax via a five-week dose escalation to 400 mg daily. Once patients reach 400 mg of venetoclax daily, patients will receive six cycles (months) of rituximab as consolidation. Total time of venetoclax therapy will be 12 cycles and total time on therapy (BR plus venetoclax plus rituximab) will be 15 cycles. Responses and endpoints will be assessed after 3, 6, 9 (laboratory only), 12, 18, 24, 30, and 36 cycles. Minimal residual disease (MRD) testing will be done after 3, 6, 9, 12, 18, and 24 cycles via an 8-color flow cytometry panel. Bone marrow testing for MRD can be performed if the peripheral blood is MRD negative (or was MRD negative at the last test). Anti-infective prophylaxis against H. zoster and P. jiroveci will be mandated. Tumor lysis syndrome (TLS) prophylaxis with allopurinol and/or an alternative will be mandated.

Conditions

• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	Bendamustine	Subjects will receive Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days.
DRUG	Venetoclax	Venetoclax: 12 cycles Venetoclax will then be started after 3 cycles of BR. Dosing for venetoclax will be in a step wise fashion as follows: * Cycle 4 days 1-7 (Week 1): 20 mg once daily * Cycle 4 days 8-14 (Week 2): 50 mg once daily * Cycle 4 days 15-21 (Week 3): 100 mg once daily * Cycle 4 days 22-28 (Week 4): 200 mg once daily * Cycle 4 day 29 and thereafter (Week 5 and on): 400 mg once daily; continue until disease progression, unacceptable toxicity, or 12 cycles duration.
DRUG	Rituximab	For cycles 1 through 3, subjects will receive BR on days 1 and 2. For cycles 5-10, subjects will receive rituximab monotherapy at 375 mg/m2 (cycle 5) or rituximab at 500 mg/m2 (cycles 6-10) on day 1 (or days 1 and 2 if split-dose).

Timeline

• Start date: 2018-11-12
• Primary completion: 2026-01-27
• Completion: 2026-01-27
• First posted: 2018-08-01
• Last updated: 2026-02-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study