Pirtobrutinib for Chronic Lymphocytic Leukemia

Recruiting at 144 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Loxo Oncology, Inc.

Must be taking: Covalent BTK inhibitors

Must not be taking: BTK degraders, Noncovalent BTK inhibitors

Disqualifiers: Richter's transformation, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

249 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Pirtobrutinib for Chronic Lymphocytic Leukemia?

Pirtobrutinib has shown high response rates in patients with chronic lymphocytic leukemia who are resistant to other BTK inhibitors, and it has been approved for use in mantle cell lymphoma. It is particularly promising for patients who need treatment after other therapies have failed, with ongoing studies to further understand its effectiveness. ^{1 2 3 4 5}

What is known about the safety of Pirtobrutinib in humans?

Pirtobrutinib has been studied for safety in patients with mantle cell lymphoma and chronic lymphocytic leukemia. Common side effects include fatigue, muscle pain, diarrhea, swelling, shortness of breath, pneumonia, and bruising. There are warnings for potential infections, bleeding, low blood cell counts, irregular heartbeats, and risk of new cancers. ^{2 3 4 6 7}

How is the drug Pirtobrutinib different from other treatments for chronic lymphocytic leukemia?

Pirtobrutinib is unique because it is a noncovalent (reversible) Bruton's tyrosine kinase inhibitor, which means it can be effective even when other similar drugs stop working. This makes it a promising option for patients who have developed resistance to existing treatments. ^{2 3 4 5 6}

What is the purpose of this trial?

The main purpose of this study is to assess the efficacy and safety of 3 dose levels of Pirtobrutinib in participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have received 1-3 lines of treatment including a covalent Bruton tyrosine kinase (BTK) inhibitor. The study is expected to last approximately 3 years.

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for people with a type of blood cancer called CLL/SLL who have tried some treatments but still need help. They should be able to take pills, had up to 3 prior treatments including a specific drug type (BTK inhibitor), and be well enough to do daily activities.

Inclusion Criteria

I have been diagnosed with CLL/SLL according to the latest criteria.

I have been treated with a BTK inhibitor.

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

Exclusion Criteria

I've had severe bleeding from a BTK inhibitor treatment.

I have been treated with specific types of medication for my condition.

My condition has progressed to a more aggressive form of cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three dose levels of Pirtobrutinib orally

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Pirtobrutinib

Trial Overview The study tests three doses of Pirtobrutinib in patients whose CLL/SLL has come back or didn't respond after treatment. It checks how well the drug works and its safety over about 3 years.

Participant Groups

Group I: Pirtobrutinib Dose 3 Experimental Treatment 1 Intervention

Pirtobrutinib administered orally.

Group II: Pirtobrutinib Dose 2 Experimental Treatment 1 Intervention

Pirtobrutinib administered orally.

Group III: Pirtobrutinib Standard Dose (Dose 1) Active Control 1 Intervention

Pirtobrutinib administered orally.

Who Is Running the Clinical Trial?

Loxo Oncology, Inc.

Lead Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Non-covalent Bruton's tyrosine kinase inhibitors (ncBTKi), like pirtobrutinib, offer a promising alternative for treating chronic lymphocytic leukemia (CLL) due to their reversible binding, which may reduce toxicity and resistance issues associated with covalent inhibitors (cBTKi).

Pirtobrutinib has demonstrated strong safety and preliminary efficacy in clinical trials for CLL, particularly for patients who have developed resistance to previous treatments, highlighting its potential role in addressing unmet needs in CLL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Covalent Bruton's Tyrosine Kinase Inhibitors in the Treatment of Chronic Lymphocytic Leukemia. Montoya, S., Thompson, MC.[2023]

Pilaralisib, a pan-PI3K inhibitor, was found to have an acceptable safety profile in a study of 25 patients with chronic lymphocytic leukemia (CLL) and lymphoma, with common side effects including diarrhea (92%) and pyrexia (52%).

The treatment showed preliminary efficacy, with 50% of CLL patients achieving a partial response and 60% experiencing significant nodal shrinkage, indicating potential for further development in these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma. Brown, JR., Davids, MS., Rodon, J., et al.[2021]

Pirtobrutinib, a noncovalent Bruton tyrosine kinase inhibitor, has shown high response rates in patients with chronic lymphocytic leukemia and mantle cell lymphoma who are resistant to conventional covalent BTK inhibitors, addressing a significant unmet need in this population.

The early studies indicate that pirtobrutinib has a favorable toxicity profile, suggesting it may be suitable for use in combination therapies, and it has recently received accelerated FDA approval for use in mantle cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. Thompson, PA., Tam, CS.[2023]

Pirtobrutinib, a noncovalent BTK inhibitor, demonstrated a 73.3% overall response rate in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously failed covalent BTK inhibitor treatments, indicating its efficacy as a new therapeutic option.

The treatment was generally well-tolerated, with only 2.8% of patients discontinuing due to adverse events, and common side effects included infections and bleeding, while serious side effects like hypertension and major hemorrhage were relatively infrequent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia. Mato, AR., Woyach, JA., Brown, JR., et al.[2023]

Pirtobrutinib received accelerated FDA approval for treating adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two prior therapies, showing a 50% overall response rate in a study of 120 patients.

While effective, pirtobrutinib has potential side effects including fatigue, diarrhea, and increased risk of infections and bleeding, necessitating postmarketing studies to further assess its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma. Telaraja, D., Kasamon, YL., Collazo, JS., et al.[2023]

In a meta-analysis of 2456 CLL patients, ibrutinib was found to have a similar risk of anemia, thrombocytopenia, and neutropenia compared to control treatments, indicating a favorable safety profile for these adverse effects.

However, patients treated with ibrutinib experienced significantly higher rates of abdominal issues and diarrhea, suggesting that while it is effective, monitoring for gastrointestinal side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials. Zhou, Y., Lu, H., Yang, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Non-Covalent Bruton's Tyrosine Kinase Inhibitors in the Treatment of Chronic Lymphocytic Leukemia. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials. [2022]