12 Participants Needed

LV20.19 CAR T-Cells + Pirtobrutinib for Lymphoma

MC
Overseen ByMedical College of Wisconsin Cancer Center Clinical Trials Office
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Medical College of Wisconsin
Must be taking: Rituximab
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for people with B-cell non-Hodgkin Lymphoma, a type of blood cancer that has not improved with other treatments. The study aims to determine if using LV20.19 CAR T-cells, a kind of engineered immune cell, with pirtobrutinib, a pill that helps stop cancer growth, is safe and effective. It seeks participants who have tried other treatments without success and are experiencing frequent relapses or disease progression. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that LV20.19 CAR T cells are generally safe. In earlier studies, most patients handled the treatment well. However, about 94% experienced cytokine release syndrome, a common reaction that usually causes fever and tiredness. Nerve-related side effects, known as neurotoxicity, occurred in 18% of patients but were mostly manageable.

For pirtobrutinib, research indicates it is also safe. Common mild side effects include high blood pressure, bruising, nausea, and diarrhea, reported by about 10% of patients. Pirtobrutinib has already been approved for other uses, suggesting it is generally well-tolerated.

Both treatments have been tested separately and found safe for many patients. This trial is the first to test them together, so careful monitoring will be important.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about LV20.19 CAR T-cells combined with Pirtobrutinib for lymphoma because they offer a novel approach compared to standard chemotherapy or antibody therapies. Unlike traditional treatments, CAR T-cells are engineered to specifically recognize and attack lymphoma cells, potentially leading to more effective targeting of the cancer. Additionally, Pirtobrutinib is an oral agent that works by inhibiting Bruton’s tyrosine kinase, a key enzyme in cancer cell survival, which could complement the action of CAR T-cells. This combination may provide a more precise and powerful attack on lymphoma, with the potential for improved outcomes and reduced side effects.

What evidence suggests that this trial's treatments could be effective for B cell malignancies?

Research has shown that LV20.19 CAR T-cell therapy, one of the treatments in this trial, has achieved remarkable results in treating relapsed or hard-to-treat mantle cell lymphoma (MCL). Studies found that all patients responded to the treatment, with 88% experiencing complete remission, meaning most showed no signs of cancer afterward.

Pirtobrutinib, the other treatment option in this trial, has proven effective for relapsed or hard-to-treat follicular lymphoma, with 52.1% of patients responding to the treatment and benefits lasting over 10 months on average. It also shows promise for patients with heavily treated mantle cell lymphoma. These treatments target B cell cancers, aiming to help patients who haven't had success with other therapies.12367

Who Is on the Research Team?

NS

Nirav Shah, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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 6 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

  • LV20.19 CAR T cells
  • Pirtobrutinib
Trial Overview The 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.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Pirtobrutinib and CAR T CellsExperimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials
645
Recruited
1,180,000+

Published Research Related to This Trial

In a study of 60 patients with relapsed diffuse large B cell lymphoma receiving CAR T therapy (axi-cel), the overall response rate was 63.3%, indicating a promising efficacy of this treatment.
The study found that responsiveness to immediate pre-CAR T chemotherapy did not significantly affect the outcomes, but patients with bulky disease before treatment had worse results, suggesting that those with known risk factors should consider interim therapies before CAR T infusion.
Predictors of response to axicabtagene-ciloleucel CAR T cells in aggressive B cell lymphomas: A real-world study.Iovino, L., Wu, QV., Voutsinas, J., et al.[2022]
A patient with primary mediastinal large B-cell lymphoma achieved a complete metabolic response after receiving pembrolizumab following relapse 3.5 months post-CD19-directed CAR T-cell therapy, indicating the potential efficacy of immune checkpoint inhibitors in this setting.
Despite achieving remission, treatment with pembrolizumab was stopped after six cycles due to pneumonitis, highlighting the importance of monitoring for side effects while using immune checkpoint inhibitors after CAR T-cell therapy.
Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review.Dimou, M., Bitsani, A., Bethge, W., et al.[2022]
In a study of 16 patients with relapsed, refractory B-cell malignancies treated with LV20.19 CAR-T therapy, the two-year progression-free survival (PFS) was 44% and overall survival (OS) was 69%, indicating promising long-term outcomes.
Factors such as lower in vivo CAR-T expansion and high metabolic tumor volume were linked to late relapse and poorer early treatment response, suggesting that these could be important predictors for patient outcomes.
Long-term outcomes and predictors of early response, late relapse, and survival for patients treated with bispecific LV20.19 CAR T-cells.Zurko, JC., Fenske, TS., Johnson, BD., et al.[2023]

Citations

Adaptive Manufacturing of LV20.19 CAR T-Cells for Relapsed ...Results: In total 17 pts with R/R MCL received LV20. 19 CAR T-cells (Phase 1=3 pts and Phase 2=14 patients).
Phase I/II Study of Adaptive Manufactured Lentiviral Anti- ...We demonstrate that on-site adaptive manufactured LV20.19 CAR T cells are feasible, safe, and efficacious for R/R MCL with best ORR of 100%, a favorable safety ...
RESULTS FROM A PHASE 1/2 STUDY OF TANDEM ...Results: To date, 14 MCL pts have received LV20.19 CAR T-cells at the target dose of 2.5x10e6 cells/kg (Phase 1=3 pts and Phase 2=11 pts).
Dual-Targeted CAR-T Therapy Shows High Response ...The median follow-up was 15.8 months. Analysis showed that the ORR was 100%, with 88% of patients reaching a complete response and 12% of ...
LV20.19 CAR T-Cell Therapy Yields 100% ORR in R ...LV20.19 CAR T-cell therapy achieved a 100% overall response rate and 88% complete response rate in relapsed/refractory MCL patients. The ...
Dual-Targeted CAR-T Therapy Shows High Response ...“Adaptively manufactured LV20.19 CAR T cells allowed rapid delivery and high efficacy, with favorable safety in patients with [relapsed/ ...
7.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/36068950/
Long-term outcomes and predictors of early response, late ...In conclusion, this initial trial of LV20. 19 CAR-T demonstrates a signal for favorable long-term outcomes for patients with R/R B-cell malignancies.
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