NCT04082897

ObinutuzuMab AtezOlizumab and VenetocLax in RichTer transfOrmation

A Multi-Center, Open Label, Uncontrolled, Phase II Clinical Trial Evaluating the Safety and Efficacy of Venetoclax in Combination With Atezolizumab and Obinutuzumab in Richter Transformation of CLL

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Niguarda Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a multicenter, open-label, uncontrolled, phase II trial aimed to establish the safety and tolerability of venetoclax, atezolizumab and obinutuzumab combination in Richter Transformation of CLL.

Detailed description

This study is a multicenter, open-label, uncontrolled, phase II trial. Initial safety run phase is designed to establish the safety and tolerability of venetoclax, atezolizumab and obinutuzumab combination. There is no dose-finding step. The doses of obinutuzumab and atezolizumab in lymphomas were previously clearly established in combination (Till BG et al. Blood 2015). It has also been shown that in a balance between efficacy and toxicity, the recommended dose of venetoclax single-agent in Follicular Lymphoma (FL) and DLBCL was 800 mg daily (Davids MS et al. JCO 2017 ). The investigators chose the lower dose level (400 mg) for this study, also corresponding to the registered one for patients with CLL, in association with two other drugs. Nine patients having achieved 9 weeks (=3 cycles) of treatment (6 doses of obinutuzumab, 3 doses of atezolizumab, 7 weeks of venetoclax) or having discontinued treatment within the first 9 weeks of treatment will be enrolled in this cohort for safety profile. If one of these 9 patients prematurely discontinue at least one of study drugs for a reason other than safety (e.g. for disease progression), he/she will be replaced. All AEs occurring during the course of the study will be captured, regardless of their intensity / grading. Grading of AEs will be completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTC-AE), version 4.0. Based on known safety profile of the 3 drugs, some adverse events of special interest will be assessed. During the initial safety run phase, all haematological toxicities and immune-related toxicities whatever the grade, and grade ≥ 2 for other toxicities will be monitored and, in this case, safety review meeting will be organized with Independent Data Monitoring Committee (IDMC) members. In case of more than 3 non-infective and non-hematologic grade ≥4 adverse events in the initial safety run cohort that according to the experience of the investigators are considered related to the combination treatment, inclusions will be stopped and IDMC members will evaluate the possibility of an early enrollment termination. The treatment schedule applied to the initial safety run cohort will be employed for the remaining patients. The 9 patients from the safety run will be included in the efficacy analysis. A response evaluation according with Lugano criteria for aggressive lymphomas (Cheson et al. JCO 2014) will be performed at the end of the sixth cycle to define treatment efficacy and, in case of achievement of 16 responses, treatment will be considered successful. The planned enrollment for this study is 28 patients. Patients will receive 35 cycles of treatment: * From cycle 1 to cycle 8 patients will receive a combination of obinutuzumab, atezolizumab and venetoclax * From cycle 9 to cycle 18 patients will receive atezolizumab and venetoclax * From cycle 19 to cycle 35 patients will receive venetoclax monotherapy.

Conditions

• CLL Transformation

Interventions

Type	Name	Description
DRUG	Obinutuzumab 25 MG/ML [Gazyva]	Obinutuzumab will be administered from C1 to C8
DRUG	Atezolizumab 60 MG/ML [Tecentriq]	Atezolizumab will be administered iv from C1 to C18
DRUG	Venetoclax Oral Tablet	Venetoclax will be administered from day 15 cycle 1) until day 21 of cycle 35

Timeline

• Start date: 2019-10-04
• Primary completion: 2026-09-01
• Completion: 2026-12-01
• First posted: 2019-09-10
• Last updated: 2024-05-28

Locations

17 sites across 2 countries: Italy, Switzerland