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Monoclonal Antibody

Roginolisib + Venetoclax + Rituximab for Chronic Lymphocytic Leukemia

Phase 1 & 2

Waitlist Available

Led By Jennifer Brown, MD, PhD

Research Sponsored by Jennifer R. Brown, MD, PhD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with relapsed/refractory CLL who meet iwCLL criteria for requiring treatment

Patients must have received at least two prior therapies for CLL including systemic therapy containing a covalent BTK inhibitor

Must not have

History of transformation of CLL to aggressive non-Hodgkin lymphoma

History or presence of cardiovascular disease, QTcF > 470 msec at screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial will investigate the safety and effectiveness of combining three drugs (Roginolisib, Venetoclax, and Rituximab) for patients with relapsed or refractory Chronic L

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include diarrhea, fatigue, nausea, low blood cell counts leading to increased infection risk or bleeding problems, allergic reactions to drug components, liver function changes, and other immune-related issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My CLL has come back or didn't respond to treatment and needs more treatment.

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

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I can do most of my daily activities by myself.

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I am 18 years or older and can consent to participate.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My heart's electrical activity is normal and I don't have heart disease.

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I do not have any active infections when starting the study treatment.

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

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I am not on high doses of steroids or immunosuppressants.

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I am taking medication that strongly affects liver enzyme CYP3A.

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I am HIV positive.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Undetectable Minimal Residual Disease(uMRD) rate by ClonoSEQ assay

Secondary study objectives

Adverse Event of Interest Rate

Complete Response Rate (CRR)

Duration of Response (DOR)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

2019

Completed Phase 3

~2200

Rituximab

1999

Completed Phase 4

~2990