Roginolisib + Venetoclax + Rituximab for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)

Overseen byJennifer R Brown, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Jennifer R. Brown, MD, PhD

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This research study will test the safety and anticancer activity of the combination of three drugs (Roginolisib, Venetoclax, and Rituximab) for participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL). The names of the study drugs involved in this study are: * Roginolisib (a novel type of PI3-kinase delta inhibitor) * Venetoclax (a type of B-cell lymphoma 2 inhibitor) * Rituximab (a type of monoclonal antibody)

Eligibility Criteria

This trial is for people with Chronic Lymphocytic Leukemia (CLL) that has come back or hasn't responded to treatment. Participants should have had at least one prior therapy and be suitable for treatment with Venetoclax and Rituximab.

Inclusion Criteria

My brain condition is stable and not causing symptoms.

I have had at least two treatments for CLL, one with a BTK inhibitor.

Willingness to use adequate contraception prior to study entry and for the duration of study participation

+9 more

Exclusion Criteria

I cannot swallow pills due to a condition in my upper GI tract.

I am not on high doses of steroids or immunosuppressants.

My CLL has transformed into a more aggressive form of lymphoma.

+15 more

Participant Groups

The study tests a combination of three drugs: Roginolisib, an experimental PI3Kδ inhibitor; Venetoclax, which targets B-cell lymphoma 2 proteins; and Rituximab, an antibody. It aims to evaluate the safety and cancer-fighting effects of this mix in CLL patients.

4Treatment groups

Experimental Treatment

Active Control

Group I: Phase 2 Arm A: Venetoclax + Roginolisib + RituximabExperimental Treatment3 Interventions

Participants will be randomized 1:1 and stratified by TP53 aberrant disease and by the number of prior therapies. * Baseline visit, imaging, bone marrow biopsy. * CT scan every 2 cycles. * Cycle 1 (5 weeks): Predetermined dose of Venetoclax 1x daily * Cycles 2 through 13: * Days 1 through 28 of 28 day cycle: Predetermined dose of Venetoclax 1x daily. * Days 1 through 28 of 28 day cycle: Predetermined dose of Roginolisib 1 x daily. * Cycles 3 through Cycle 8: --Day 1 of 28 day cycle: Predetermined dose of Rituximab once. * End of treatment visit * Follow up visits for up to 5 years

Group II: Phase 1b Arm B: Venetoclax + Roginolisib + Rituximab Dose Level 1Experimental Treatment3 Interventions

* Baseline visit, imaging, bone marrow biopsy * CT scan every 2 cycles * Cycle 1 (5 weeks): Predetermined dose of Venetoclax 1x daily * Cycle 2: Days 1 through 28 of 28 day cycle: Predetermined dose of Venetoclax 1x daily and predetermined dose of Roginolisib 1 x daily --If 0 of 3 participants do not experience a DLT, Phase 2 will start at this dose level. If 1 of 3 participants experience a DLT, 3 more participants will be enrolled, and if 1 of those 6 participants experience a DLT, this dose level will be used for Phase 2. If a DLT is observed in 2 of those 6, de-escalate to Dose Level -1. * Cycles 3 through Cycle 8: Day 1 of 28 day cycle: Predetermined dose of Rituximab once * Cycles 3 through 13: Days 1 through 28 of 28 day cycle: Predetermined dose of Venetoclax 1x daily and predetermined dose of Roginolisib 1 x daily * End of treatment visit * Follow up visits for up to 5 years

Group III: Phase 1b Arm A: Venetoclax + Roginolisib + Rituximab Dose Level -1Experimental Treatment3 Interventions

3+3 design to establish a Recommended Phase 2 Dose (RP2D) for Roginolisib, starting at Dose Level -1. * Baseline visit, imaging, bone marrow biopsy * CT scan every 2 cycles * Cycle 1 (5 weeks): Predetermined dose of Venetoclax 1x daily * Cycle 2: Days 1 through 28 of 28 day cycle: Predetermined dose of Venetoclax 1x daily and predetermined dose of Roginolisib 1 x daily --If 0 of 3 participants do not experience a dose-limiting toxicity (DLT), the study will proceed. If 1 of 3 participants experience a DLT, 3 more participants will be enrolled, and if 1 of those 6 participants experience a DLT, this is the RP2D for phase 2. If a DLT is observed in 2 of 3 or 2 of 6, the study will be stopped. * Cycles 3 through Cycle 8: Day 1 of 28 day cycle: Predetermined dose of Rituximab once * Cycles 3 through 13: Days 1 through 28 of 28 day cycle: Predetermined dose of Venetoclax 1x daily and predetermined dose of Roginolisib 1 x daily * End of treatment visit * Follow up visits for up to 5 years

Group IV: Phase 2 Arm B: Venetoclax + RituximabActive Control2 Interventions

Participants will be randomized 1:1 and stratified by TP53 aberrant disease and by the number of prior therapies. * Baseline visit, imaging, bone marrow biopsy. * CT scan every 2 cycles. * Cycle 1 (5 weeks): Predetermined dose of Venetoclax 1x daily * Cycles 2 through 13: --Days 1 through 28 of 28 day cycle: Predetermined dose of Venetoclax 1x daily. * Cycle 3 through 8: --Day 1 of 28 day cycle: Predetermined dose of Rituximab once. * End of treatment visit * Follow up visits for up to 5 years

Rituximab is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Rituxan for: