60 Participants Needed

Pirtobrutinib + CAR T-cell Therapy for Mantle Cell Lymphoma

Recruiting at 2 trial locations
RC
Overseen ByRuthie Chae
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This is a phase 2, open-label, randomized, multicenter clinical trial in patients with relapsed/refractory mantle cell lymphoma (R/R MCL) who meet the criteria for standard-of-care FDA label for CD19 CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel).

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications before joining the trial. There are specific 'washout' periods (time without taking certain medications) required for different types of treatments, such as 2 weeks for targeted agents or 3 months for bendamustine. Please consult with the trial team for guidance on your specific medications.

What data supports the effectiveness of the treatment Pirtobrutinib + CAR T-cell Therapy for Mantle Cell Lymphoma?

Research shows that brexucabtagene autoleucel (a type of CAR T-cell therapy) has been associated with improved survival in patients with relapsed or refractory mantle cell lymphoma who had previous treatment with Bruton tyrosine kinase inhibitors. Additionally, pirtobrutinib, a noncovalent Bruton tyrosine kinase inhibitor, has shown promising effectiveness in patients with poor prognosis B-cell malignancies, including those who have previously been treated with other BTK inhibitors.12345

What safety data exists for Pirtobrutinib and Brexucabtagene Autoleucel in treating Mantle Cell Lymphoma?

Pirtobrutinib has been associated with side effects like fatigue, muscle pain, diarrhea, swelling, shortness of breath, pneumonia, and bruising. There are warnings for infections, bleeding, low blood cell counts, irregular heartbeats, and potential for other cancers. Brexucabtagene autoleucel has shown improved survival rates in patients with relapsed or refractory mantle cell lymphoma, but specific safety data is not detailed in the provided articles.12678

What makes the Pirtobrutinib + CAR T-cell Therapy unique for treating mantle cell lymphoma?

This treatment is unique because it combines Pirtobrutinib, a noncovalent Bruton tyrosine kinase inhibitor (BTKi) effective in patients resistant to other BTK inhibitors, with CAR T-cell therapy, which uses modified immune cells to target cancer. This combination offers a novel approach for patients with relapsed or refractory mantle cell lymphoma who have limited options.3691011

Research Team

Michael Jain | Moffitt

Michael Jain, MD, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for people with a type of lymphoma called relapsed/refractory mantle cell lymphoma (R/R MCL) who qualify for standard CD19 CAR T-cell therapy. Specific eligibility details are not provided, but typically participants need to meet certain health standards and have no conflicting conditions.

Inclusion Criteria

I have followed the required waiting period before undergoing leukapheresis.
Must have ability to comprehend and the willingness to sign written informed consent for study participation
Patients must meet specific laboratory parameters at screening
See 5 more

Exclusion Criteria

I have been treated with pirtobrutinib for more than 2 months before joining this study.
My Mantle Cell Lymphoma has spread to my brain or spinal cord.
Participants who have not recovered from adverse events (AEs) due to prior anticancer therapy
See 23 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bridging Therapy

Participants receive pirtobrutinib as bridging therapy from day -27 to day -7

3 weeks

CAR T-cell Therapy

Participants receive CD19 CAR T-cell therapy with brexucabtagene autoleucel

1 day

Post-Therapy Monitoring

Participants are monitored for severe ICANS and CRS in the first 60 days after CAR T infusion

8 weeks

Follow-up

Participants are monitored for progression-free survival and overall survival

12 months

Long-term Follow-up

Participants are monitored for overall response rate and overall survival

48 months

Treatment Details

Interventions

  • Brexucabtagene Autoleucel
  • Pirtobrutinib
Trial OverviewThe study is testing two treatments: Brexucabtagene Autoleucel, a form of CAR T-cell therapy, and Pirtobrutinib, a medication. It's an open-label trial where patients are randomly assigned to receive one of these interventions.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm BExperimental Treatment2 Interventions
Participants will recieve pirtobrutinib as bridging therapy from day -27 to day -7. Participants on Arm B (n=30) will discontinue pirtobrutinib after day -7 and will not receive concurrent pirtobrutinib ("con-none") between day -6 and 1-year post-CD19 CAR T-cell therapy.
Group II: Arm AExperimental Treatment2 Interventions
Participants will recieve pirtobrutinib as bridging therapy from day -27 to day -7. Participants randomized to Arm A (n=30) will continue to receive concurrent pirtobrutinib ("con-pirto"), starting at day -6 and continued until 1-year post-CD19 CAR T-cell therapy with brexucel.

Brexucabtagene Autoleucel is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Tecartus for:
  • Mantle cell lymphoma (MCL)
  • Acute lymphoblastic leukemia (ALL)
🇺🇸
Approved in United States as Tecartus for:
  • Mantle cell lymphoma (MCL)
  • Acute lymphoblastic leukemia (ALL)

Find a Clinic Near You

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials
576
Recruited
145,000+

Eli Lilly and Company

Industry Sponsor

Trials
2,708
Recruited
3,720,000+
Dr. Daniel Skovronsky profile image

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks profile image

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Bankhead-Coley Florida Biomedical Research Program

Collaborator

Trials
3
Recruited
280+

Findings from Research

A large multicenter retrospective analysis of patients with mantle cell lymphoma who had previously failed Bruton tyrosine kinase inhibitors (BTKis) provides important outcome data that can serve as a benchmark for future studies.
The study highlights the significant challenges in managing patients with relapsed or refractory mantle cell lymphoma, indicating a need for improved treatment strategies, especially before the introduction of new therapies like brexucabtagene autoleucel (Tecartus).
Post-BTK inhibitor mantle cell lymphoma: When is CAR-T not the answer?McCulloch, R.[2023]
In patients with relapsed/refractory mantle cell lymphoma (MCL) who previously failed a Bruton tyrosine kinase inhibitor, brexucabtagene autoleucel (brexu-cel) showed significantly improved overall survival compared to standard of care treatments, with hazard ratios indicating a strong survival benefit.
The analysis used multiple methods to adjust for differences in patient characteristics, consistently showing that brexu-cel led to better outcomes, highlighting its potential as an effective therapy for this challenging patient population.
Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma.Hess, G., Dreyling, M., Oberic, L., et al.[2023]
Idelalisib, a PI3Kδ inhibitor, has shown effectiveness in patients with mantle cell lymphoma who have undergone extensive prior treatments.
This suggests that idelalisib could be a promising therapeutic option for patients with difficult-to-treat mantle cell lymphoma.
Idelalisib has activity in mantle cell lymphoma.[2019]

References

Post-BTK inhibitor mantle cell lymphoma: When is CAR-T not the answer? [2023]
Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. [2023]
Idelalisib has activity in mantle cell lymphoma. [2019]
BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naive mantle cell lymphoma. [2023]
New Directions for Mantle Cell Lymphoma in 2022. [2022]
Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed/refractory mantle cell lymphoma. [2023]
Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell Therapy for the Treatment of Mantle Cell Lymphoma. [2022]
FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma. [2023]
Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma. [2023]
11.United Arab Emiratespubmed.ncbi.nlm.nih.gov
Pirtobrutinib: First Non-covalent Tyrosine Kinase Inhibitor for Treating Relapsed or Refractory Mantle Cell Lymphoma in Adults. [2023]