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

Trial Summary

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.

What evidence supports the effectiveness of the drug combination of Pacritinib and BTK Inhibitor for treating Mantle Cell Lymphoma?

BTK inhibitors like ibrutinib and acalabrutinib have shown effectiveness in treating mantle cell lymphoma by targeting specific cancer cell pathways, and combining them with other drugs like Pacritinib may enhance treatment outcomes. Although Pacritinib is not specifically mentioned in the studies, the combination of BTK inhibitors with other agents has been explored to improve response rates in similar conditions. ^{1 2 3 4 5}

What safety data exists for Pacritinib and BTK inhibitors in humans?

BTK inhibitors, like ibrutinib and acalabrutinib, have been associated with side effects such as bleeding, atrial fibrillation (irregular heartbeat), and increased risk of infection. Pirtobrutinib, another BTK inhibitor, is generally well tolerated but can cause fatigue, muscle pain, diarrhea, and bruising. Pacritinib, marketed as Vonjo, has been studied for other conditions, but specific safety data for its combination with BTK inhibitors in mantle cell lymphoma is not detailed in the provided research. ^{2 3 6 7 8}

How is the drug Pacritinib + BTK Inhibitor unique for treating Mantle Cell Lymphoma?

The combination of Pacritinib, a drug known for its use in other conditions, with a BTK inhibitor offers a novel approach for treating Mantle Cell Lymphoma by potentially enhancing the effectiveness of BTK inhibition, which is a key target in this type of cancer. This combination may provide a new option for patients who have not responded well to existing treatments. ^{1 2 3 4 9}

What is the purpose of this trial?

This phase I trial tests the safety and side effects of pacritinib in combination with a Bruton's tyrosine kinase (BTK) inhibitor and how well it works in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Pacritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. BTK inhibitors block a protein called BTK which is present on B-cell (a type of white blood cell) cancers such as mantle cell lymphoma at abnormal levels. This may help keep tumor cells from growing and spreading. Giving pacritinib in combination with a BTK inhibitor may be safe, tolerable and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Research Team

Tycel J Phillips

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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.

I have an active HIV infection.

Pregnancy or breastfeeding

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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]

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, 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]

References

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

Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma. [2021]

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

Bruton tyrosine kinase inhibitors for the treatment of mantle cell lymphoma: review of current evidence and future directions. [2021]

3. England 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. [2023]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Use of BTK inhibitors with focus on ibrutinib in mantle cell lymphoma: An expert panel opinion statement. [2022]

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

Drug interactions with Bruton's tyrosine kinase inhibitors: clinical implications and management. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Zanubrutinib in lymphoproliferative disorders: a comprehensive review. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed/refractory mantle cell lymphoma. [2023]