Pacritinib + BTK Inhibitor for Mantle Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: BTK inhibitors

Must not be taking: JAK2 inhibitors, Pirtobrutinib

Disqualifiers: Recent stem cell transplant, Cardiovascular disease, Active infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effects of combining pacritinib, a drug that may stop tumor growth by interfering with necessary enzymes, with a BTK inhibitor, which blocks a protein involved in cancer growth, to treat mantle cell lymphoma that has returned or isn't responding to previous treatments. This combination could potentially be effective. Suitable participants have mantle cell lymphoma that has recurred or resisted treatment and are currently taking a BTK inhibitor like ibrutinib. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you continue taking a BTK inhibitor like ibrutinib, acalabrutinib, or zanubrutinib. However, you may need to stop taking certain other medications, such as strong CYP3A4 inducers/inhibitors, medications that increase bleeding risk, and those with arrhythmogenic potential, at least 14 days before starting the trial. Always discuss with the study team to understand specific requirements for your situation.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pacritinib is generally safe for patients with certain blood disorders. Studies have found it to have a good safety record, with some patients experiencing mild to moderate side effects, such as stomach issues.

BTK inhibitors, a type of cancer treatment, are commonly used for treating mantle cell lymphoma. They have been well-researched and are known to be effective, although they can also cause side effects. Many reports have noted common side effects, including fatigue and nausea.

Overall, both treatments have been studied for safety in other conditions. This trial represents an early step in determining if these treatments can be used safely together for mantle cell lymphoma. ^{1 2 3 4 5}

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown pacritinib to be generally safe, with many experiencing only mild to moderate side effects, such as stomach problems. It was also safe for individuals with long-term health issues. BTK inhibitors, commonly used to treat certain cancers, are known for their safety, though they can cause serious side effects at higher doses. Both treatments have been used safely before. However, this trial remains in its early stages, so researchers are primarily focused on assessing the safety of this combination for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Pacritinib with a BTK inhibitor for treating Mantle Cell Lymphoma because this approach offers a novel mechanism of action. While the current standard of care typically involves BTK inhibitors alone, Pacritinib introduces a JAK2/FLT3 inhibition which might enhance the treatment's efficacy. This combination could potentially target the cancer cells more effectively, offering hope for improved outcomes in patients who may not respond to BTK inhibitors alone.

What evidence suggests that pacritinib combined with a BTK inhibitor might be an effective treatment for mantle cell lymphoma?

Research has shown that BTK inhibitors hold promise in treating mantle cell lymphoma (MCL). In one study, 70% of patients who fully responded to treatment remained free from disease progression after two years, and 90% were still alive. Another study found that the average survival time for patients treated with BTK inhibitors was about 35 months. In this trial, participants will receive a combination of Pacritinib and a BTK inhibitor. Pacritinib, a newer drug in this combination, blocks certain enzymes that help cancer cells grow. Using Pacritinib with BTK inhibitors might be more effective because it attacks cancer cells in different ways. These findings suggest possible benefits for patients whose MCL has returned or not responded to other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Tycel J Phillips

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with Mantle Cell Lymphoma that has either returned after treatment or hasn't responded to previous treatments. Participants should be suitable for biopsies and imaging tests like PET and CT scans.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

Specific ANC and platelet count requirements

I am able to get out of my bed or chair and move around.

Exclusion Criteria

I have had a stem cell transplant from a donor.

Pregnancy or breastfeeding

I have an active HIV infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pacritinib orally twice daily on days 1-28 of each cycle, with cycles repeating every 28 days in the absence of disease progression or unacceptable toxicity. Patients also continue to receive a BTK inhibitor per standard of care.

Up to 12 months

Regular visits for blood sample collection, optional tissue biopsy, bone marrow biopsy and aspiration, and PET/CT

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Patients are followed up at 30 days post-treatment and every 3 months if no progression is observed.

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• BTK Inhibitor
• Pacritinib

Trial Overview The trial is testing the safety and effectiveness of pacritinib combined with a BTK inhibitor, both aimed at stopping tumor growth by targeting specific enzymes and proteins in white blood cells.

How Is the Trial Designed?

Group I: Treatment (pacritinib, BTK inhibitor) Experimental Treatment 8 Interventions

Patients receive pacritinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also continue to receive BTK inhibitor per standard of care. Additionally, patients undergo blood sample collection, optional tissue biopsy, bone marrow biopsy and aspiration and PET/CT throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ibrutinib and acalabrutinib are effective BTK inhibitors that have been approved for treating relapsed or refractory mantle cell lymphoma (MCL), showing significant therapeutic benefits in clinical trials.

Acalabrutinib has a greater selectivity for BTK compared to ibrutinib, which reduces the risk of certain side effects like atrial fibrillation, although both drugs can still cause headaches and other toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bruton tyrosine kinase inhibitors for the treatment of mantle cell lymphoma: review of current evidence and future directions. Bond, DA., Alinari, L., Maddocks, K.[2021]

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]

Pirtobrutinib is a noncovalent Bruton tyrosine kinase inhibitor that effectively targets both normal and mutant forms of BTK, showing promise in treating relapsed mantle cell lymphoma, especially in patients who have not previously received BTK inhibitors.

This ongoing phase III study aims to determine if pirtobrutinib is more effective than existing covalent BTK inhibitors in patients with previously treated mantle cell lymphoma, highlighting its potential as a new treatment option for those with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naive mantle cell lymphoma. Eyre, TA., Shah, NN., Dreyling, M., et al.[2023]

Pirtobrutinib, a new non-covalent Bruton's tyrosine kinase inhibitor, has shown a 52% overall response rate in patients with relapsed/refractory mantle cell lymphoma, demonstrating its efficacy in a heavily pre-treated population.

The drug was well-tolerated with no maximum tolerated dose identified in the initial trials, although neutropenia was the most common serious side effect, indicating a favorable safety profile for patients resistant to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed/refractory mantle cell lymphoma. Davis, DD., Ohana, Z., Pham, HM.[2023]

Pirtobrutinib, approved by the FDA in January 2023, is specifically designed to treat relapsed or refractory mantle cell lymphoma, especially in patients who have developed resistance to other BTK inhibitors like ibrutinib.

Unlike traditional covalent BTK inhibitors, pirtobrutinib offers a new treatment option with potentially fewer off-target side effects, making it a promising alternative for patients facing limitations with existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirtobrutinib: First Non-covalent Tyrosine Kinase Inhibitor for Treating Relapsed or Refractory Mantle Cell Lymphoma in Adults. De, SK.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5912680/

Outcomes in 370 patients with mantle cell lymphoma treated ... In patients who achieved a CR with ibrutinib, 70% were progression-free and 90% were alive at 2 years. These data would support the concept of combination ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2473952922003287

Evaluating real-world treatment patterns and outcomes of ... Among patients treated with BTK inhibitors, the median real-world overall survival (rwOS) was 35 months (95% confidence interval [CI], 27-50), ...

3. haematologica.org haematologica.org/article/view/haematol.2022.282469

Final results and overall survival data from a phase II study ... The 5-year overall survival (OS) rate for patients with high-risk MIPI score has been reported to be 35% compared with 81% and 63% for those ...

4. becarispublishing.com becarispublishing.com/digital-content/blog-post/mantle-cell-lymphoma-real-world-treatment-patterns-and-outcomes-focus-btk-inhibitors

Mantle cell lymphoma real-world treatment patterns and ... Among patients treated with BTK inhibitors, the median real-world overall survival was 35 months (95% CI, 27-50), 24 months (95% CI, 22-30), and ...

5. ashpublications.org ashpublications.org/bloodneoplasia/article/2/3/100128/537696/Real-world-outcomes-with-ibrutinib-in-relapsed-or

Real-world outcomes with ibrutinib in relapsed or refractory ... In conclusion, real-world outcomes after initiation of ibrutinib for R/R MCL were poorer than observed in clinical trials, and dose-limiting ...

6. haematologica.org haematologica.org/article/view/haematol.2023.284896

Safety and efficacy of acalabrutinib plus bendamustine and ... BTK inhibitors have led to a paradigm shift in the treatment of MCL and have become standard treatments in the R/R MCL setting. Acalabrutinib (A) ...

7. ascopubs.org ascopubs.org/doi/10.1200/EDBK_349509

New Directions for Mantle Cell Lymphoma in 2022 The median progression-free survival (PFS) rates were 6.5 months, 5 months, and 4 months, respectively. Overall, these results demonstrate that ...

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.995522/full

Data mining and safety analysis of BTK inhibitors Results: In total, 43,429 reports of ibrutinib were extracted and 1527 AEs were identified, whereas 1742 reports of acalabrutinib were extracted ...