~8 spots leftby Jul 2026

LV20.19 CAR T-Cells + Pirtobrutinib for Lymphoma

Recruiting in Palo Alto (17 mi)
NS
Overseen byNirav Shah, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Medical College of Wisconsin
Must be taking: Rituximab
Must not be taking: Anticoagulants, Antibodies
Disqualifiers: Hepatitis, Autoimmune disease, CNS involvement, others
No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a phase I, interventional, single arm, open label, treatment study designed to evaluate the safety and efficacy of LV20.19 CAR -T cells with pirtobrutinib bridging and maintenance in adult patients with B cell malignancies that have failed prior therapies.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some treatments before starting the study. Specifically, targeted agents, investigational agents, therapeutic monoclonal antibodies, or cytotoxic chemotherapy must be stopped for 5 half-lives or 2 weeks, whichever is shorter. Additionally, certain treatments like anti-CD20 and anti-CD19 antibodies must be stopped 4 weeks before cell infusion.

What data supports the effectiveness of the treatment LV20.19 CAR T-Cells + Pirtobrutinib for Lymphoma?

CAR T-cell therapy, like the LV20.19 CAR T-cells, has shown promise in treating aggressive B-cell lymphomas, with studies indicating significant response rates in patients with relapsed or refractory conditions. Additionally, similar CAR T-cell therapies have been effective in improving survival rates in patients with large B-cell lymphomas.12345

Is the combination of LV20.19 CAR T-Cells and Pirtobrutinib safe for humans?

CAR T-cell therapies, like LV20.19, have been used safely in humans, but they can cause serious side effects such as cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). Pirtobrutinib, a type of drug called a Bruton tyrosine kinase inhibitor, is being studied in combination with CAR T-cells to improve safety and effectiveness, but specific safety data for this combination is not yet available.678910

How is the LV20.19 CAR T-Cells + Pirtobrutinib treatment different from other treatments for lymphoma?

The LV20.19 CAR T-Cells + Pirtobrutinib treatment is unique because it combines a bispecific CAR T-cell therapy targeting both CD19 and CD20, which may improve long-term outcomes for patients with relapsed or refractory B-cell malignancies. This dual targeting approach is different from traditional CAR T-cell therapies that typically target only one antigen, potentially reducing the risk of relapse due to antigen loss.23111213

Research Team

NS

Nirav Shah, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

Adults aged 18-80 with B-cell non-Hodgkin Lymphoma that's come back or didn't respond to treatment. They must have tried at least two therapies, including a BTK inhibitor and anti-CD20 antibody for certain types. Those who've had previous transplants or CAR T-cell therapy may qualify, but there are limits on the latter.

Inclusion Criteria

I have been diagnosed with Mantle Cell Lymphoma.
My condition is DLBCL or a related subtype.
My condition worsened after 2nd line BTK inhibitor treatment.
See 7 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bridging Treatment

Pirtobrutinib is administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion

2 weeks

CAR T-Cell Infusion

LV20.19 CAR T cells are administered either fresh or thawed after cryopreservation by IV injection

1 day
1 visit (in-person)

Initial Follow-up

Participants are monitored for adverse events with grade 3 to 5 severity during the first 28 days following CAR T-cell infusion

4 weeks

Maintenance Treatment

Pirtobrutinib is administered again at 200 mg/day orally from day 28-120 for up to one year as maintenance post cell infusion

up to 1 year

Long-term Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • LV20.19 CAR T cells (CAR T-cell Therapy)
  • Pirtobrutinib (Other)
Trial OverviewThe trial is testing LV20.19 CAR T-cells combined with Pirtobrutinib in patients whose lymphoma has resisted other treatments. It's an early-phase study checking if this combo is safe and works well as a bridge and ongoing therapy.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Pirtobrutinib and CAR T CellsExperimental Treatment2 Interventions
Pirtobrutinib is an oral agent. LV20.19 CAR T cells will be administered either fresh or thawed after cryopreservation by IV injection.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials
645
Recruited
1,180,000+
Dr. Joseph E. Kerschner profile image

Dr. Joseph E. Kerschner

Medical College of Wisconsin

Chief Medical Officer since 2011

MD, specific institution not identified

Dr. John R. Raymond, Sr. profile image

Dr. John R. Raymond, Sr.

Medical College of Wisconsin

Chief Executive Officer since 2010

MD from the Medical University of South Carolina

Findings from Research

In a study of 22 patients with relapsed/refractory non-Hodgkin lymphoma who received a combination treatment of lenalidomide and rituximab, all patients who underwent stem cell transplantation (SCT) achieved a complete response.
Patients with large B-cell lymphoma (LBCL) who underwent SCT after the combination treatment had significantly better outcomes in terms of response duration, progression-free survival, and overall survival compared to those who did not undergo SCT.
Clinical outcomes of a novel combination of lenalidomide and rituximab followed by stem cell transplantation for relapsed/refractory aggressive B-cell non-hodgkin lymphoma.Cai, Q., Chen, Y., Zou, D., et al.[2021]
CAR19-engineered invariant natural killer T (iNKT) cells show enhanced anti-lymphoma activity compared to traditional CAR19-T cells, leading to improved tumor-free and overall survival in both laboratory and animal studies.
The combination of CAR19-iNKT cells with all-trans retinoic acid further boosts their effectiveness against CD19+ chronic lymphocytic leukemia, suggesting a promising new approach for treating lymphomas and potentially other cancers that express CD1d.
Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.Rotolo, A., Caputo, VS., Holubova, M., et al.[2021]
Anti-CD19 CAR-T therapy has been approved for patients with relapsed/refractory diffuse large B cell lymphoma, showing promising clinical outcomes based on recent trials like ZUMA-1, JULIET, and TRANSCEND NHL-001.
Healthcare providers need to understand the indications, potential toxicities, and limitations of this therapy to effectively manage patient referrals and treatment plans.
Anti-CD19 Chimeric Antigen Receptor T Cell Therapies: Harnessing the Power of the Immune System to Fight Diffuse Large B Cell Lymphoma.Havard, R., Stephens, DM.[2020]

References

Clinical outcomes of a novel combination of lenalidomide and rituximab followed by stem cell transplantation for relapsed/refractory aggressive B-cell non-hodgkin lymphoma. [2021]
Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. [2021]
Anti-CD19 Chimeric Antigen Receptor T Cell Therapies: Harnessing the Power of the Immune System to Fight Diffuse Large B Cell Lymphoma. [2020]
Predictors of response to axicabtagene-ciloleucel CAR T cells in aggressive B cell lymphomas: A real-world study. [2022]
Safety and efficacy of axicabtagene ciloleucel in refractory large B-cell lymphomas. [2020]
CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies. [2019]
Current combinatorial CAR T cell strategies with Bruton tyrosine kinase inhibitors and immune checkpoint inhibitors. [2022]
Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]
Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma. [2020]
10.United Statespubmed.ncbi.nlm.nih.gov
Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review. [2022]
CAR-T 19 combined with reduced-dose PD-1 blockade therapy for treatment of refractory follicular lymphoma: A case report. [2020]
Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review. [2022]
13.United Statespubmed.ncbi.nlm.nih.gov
Long-term outcomes and predictors of early response, late relapse, and survival for patients treated with bispecific LV20.19 CAR T-cells. [2023]