What is the mechanism of action of this treatment?

The most common treatments for Chronic Lymphocytic Leukemia (CLL) include Bruton tyrosine kinase (BTK) inhibitors like pirtobrutinib and the combination of bendamustine and rituximab. BTK inhibitors work by blocking the BTK enzyme, which is essential for B-cell receptor signaling, thereby reducing the survival and proliferation of CLL cells. Bendamustine induces DNA damage, leading to cell death, while rituximab targets the CD20 protein on B-cells, marking them for destruction by the immune system. These mechanisms are crucial for CLL patients as they help in tailoring treatment strategies based on the disease's specific characteristics and managing potential side effects effectively.

What side effects are associated with this type of intervention?

BTK inhibitors like Pirtobrutinib commonly cause non-hematologic side effects such as diarrhea, peripheral edema, dry eye, arthralgia, hypertension, atrial fibrillation, and major hemorrhage, with less frequent hematologic effects like neutropenia. Bendamustine and Rituximab (BR) therapy is associated with hematologic toxicities including severe neutropenia and infections, and non-hematologic toxicities such as nausea, vomiting, and fatigue. Each treatment has a distinct side effect profile, with BTK inhibitors generally causing more non-hematologic side effects and BR therapy causing more hematologic side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Lymphocytic Leukemia (CLL) that are similar to those being studied in the trial of Pirtobrutinib versus Bendamustine and Rituximab. Bruton tyrosine kinase (BTK) inhibitors such as Ibrutinib and Acalabrutinib have been approved for CLL due to their efficacy in targeting the BTK pathway. Additionally, combination therapies like Bendamustine plus Rituximab (BR) have been approved, leveraging the DNA-damaging effects of Bendamustine and the CD20-targeting action of Rituximab. These treatments have shown significant efficacy in managing CLL, providing multiple therapeutic options for patients.

What other types of research exist?

Promising alternatives for CLL treatment in 2024 include: 1) Ibrutinib, a BTK inhibitor, which has shown superior progression-free survival (PFS) and overall survival (OS) in various trials, especially in combination with venetoclax or obinutuzumab. 2) Venetoclax, a BCL-2 inhibitor, often combined with obinutuzumab, which has demonstrated high rates of complete remission and undetectable minimal residual disease (uMRD). 3) Acalabrutinib, another BTK inhibitor, which is effective and has a favorable safety profile, particularly in combination with venetoclax and obinutuzumab. These alternatives offer significant efficacy and manageable toxicity profiles, making them strong candidates for CLL treatment.

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Alkylating agent

Pirtobrutinib vs BR for Leukemia (BRUIN CLL-313 Trial)

Phase 3

Waitlist Available

Research Sponsored by Loxo Oncology, Inc.

Eligibility Criteria Checklist

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

Must have

Confirmed diagnosis of CLL/SLL requiring therapy, per iwCLL 2018 criteria

Kidney function: Estimated creatinine clearance ≥40 mL/min

Must not have

Presence of 17p deletion

Active hepatitis B or hepatitis C

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares a new drug, Pirtobrutinib, with an existing treatment, BR, in patients with CLL/SLL who have not been treated before. Pirtobrutinib works by blocking a protein that helps cancer cells grow, while BR damages cancer cells and helps the immune system destroy them.

Who is the study for?

This trial is for untreated patients with CLL/SLL who need therapy. They must have a certain level of blood cells and organ function, no severe allergies to the drugs being tested, no active hepatitis B/C or HIV, and not be on other cancer treatments or recent live vaccines.

What is being tested?

The study compares Pirtobrutinib (LOXO-305) against Bendamustine plus Rituximab in treating CLL/SLL. Participants will receive one of these treatments randomly and their health outcomes will be monitored for up to five years.

What are the potential side effects?

Possible side effects include allergic reactions to medication components, potential bone marrow suppression leading to low blood cell counts, risk of infections due to weakened immune system, and various organ-specific inflammations.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with CLL/SLL and need treatment.

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My kidneys work well enough (creatinine clearance ≥40 mL/min).

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

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

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My cancer has a 17p deletion.

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I have active hepatitis B or C.

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I do not have any ongoing serious infections.

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My cancer has spread to my brain or spinal cord.

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I need blood thinners like warfarin for my condition.

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I am HIV positive.

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My condition has transformed into a more aggressive form known as Richter's syndrome.

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I have received treatment for CLL/SLL before.

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I am not using any experimental drugs or cancer treatments, except for hormone therapy.

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I have a serious heart condition.

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I do not have an active, uncontrolled autoimmune blood disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 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

To evaluate progression-free survival (PFS) of pirtobrutinib (Arm A) compared to bendamustine and rituximab (Arm B)

Secondary study objectives

To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms

To evaluate the effectiveness of Arm A compared to Arm B in patient-reported physical functioning

To evaluate the effectiveness of Arm A compared to Arm B: Duration of Response (DOR)

+4 more

Side effects data

From 2022 Phase 1 trial • 32 Patients • NCT05176314

Petechiae

Headache

100%

80%

60%

40%

20%

Study treatment Arm

200 mg Pirtobrutinib QD (Days 7-12)

20 mg Rosuvastatin (Day 1)

200 mg Pirtobrutinib QD (Days 14-17)

20 mg Rosuvastatin + 200 mg Pirtobrutinib (Day 13)

20 mg Rosuvastatin + 200 mg Pirtobrutinib (Day 6)

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm A (Pirtobrutinib)Experimental Treatment1 Intervention

Pirtobrutinib administered orally

Group II: Arm B (BR)Active Control2 Interventions

Bendamustine plus rituximab administered intravenously (IV)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pirtobrutinib

2020

Completed Phase 1

~240

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Lymphocytic Leukemia (CLL) include Bruton tyrosine kinase (BTK) inhibitors like pirtobrutinib and the combination of bendamustine and rituximab. BTK inhibitors work by blocking the BTK enzyme, which is essential for B-cell receptor signaling, thereby reducing the survival and proliferation of CLL cells. Bendamustine induces DNA damage, leading to cell death, while rituximab targets the CD20 protein on B-cells, marking them for destruction by the immune system. These mechanisms are crucial for CLL patients as they help in tailoring treatment strategies based on the disease's specific characteristics and managing potential side effects effectively.

Phase 2, multicenter GIBB study of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia.