LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies

NCT05990465 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PRO00050826
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Mantle Cell Lymphoma; Burkitt Lymphoma

Keywords

CAR-T; Chimeric antigen receptor T-cell therapy; CAR Therapy; Pirtobrutinib; B Cells; BTK inhibitor; Bruton's tyrosine kinase

Outcome Measures

Primary Outcomes (3)

• Number of Adverse Events After CAR 20/19-T Cell Infusion

  This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5) occurring during the first 28 days following infusion.

  Up until 28 days after infusion

• Number of Adverse Events After Pirtobrutinib Administration in Part A

  Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).

  14 days prior to apheresis until the start of lymphodepletion

• Number of Adverse Events After Pirtobrutinib Administration in Part B

  Pirtobrutinib will be started again at 200 mg/day orally on day 28-120 for up to one year as maintenance post cell infusion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).

  Day 28 until up to one year

Study Arms (1)

Pirtobrutinib and CAR T Cells

EXPERIMENTAL

Pirtobrutinib is an oral agent. LV20.19 CAR T cells will be administered either fresh or thawed after cryopreservation by IV injection.

Drug: Pirtobrutinib; Drug: LV20.19 CAR T cells

Interventions

Pirtobrutinib DRUG

Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion and restarted between day 28-120 for up to one year as maintenance post cell infusion.

Also known as: Jaypirca, LOXO-305

Pirtobrutinib and CAR T Cells

LV20.19 CAR T cells DRUG

Subjects will receive a dose of 2.5x10\^6 CAR-T cells/kg as a previously identified safe in a Phase 1 protocol at the Medical College of Wisconsin.

Pirtobrutinib and CAR T Cells

Eligibility Criteria

• Age: 18 Years - 81 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be aged ≥18 years and \<81 years with relapsed or refractory B-cell non-Hodgkin Lymphoma (NHL).
• Diagnosis of relapsed or refractory B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), Mantle Cell Lymphoma, Burkitt Lymphoma and DLBCL with associated subtypes (aggressive B-cell lymphoma, high grade B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, Epstein-Barr virus-positive (EBV)+ diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone, and Richter's transformation).
• Disease specific criteria as follows:
• DLBCL and associated subtypes (listed above)
• i. Must have received Rituximab or another cluster of differentiation 20 (CD20) antibody with combination anthracycline based chemotherapy regimen and have ONE of the following:
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• Primary refractory lymphoma or early relapse ≤6 months after one line of therapy.
• For relapse \>6.00 months, failure of two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant.
• ii. Relapse post-autologous transplant. iii. Relapse post-allogeneic transplant. iv. Relapse post-CAR T-cell therapy (maximum 2 patients allowed with this designation).
• b. Mantle Cell Lymphoma
• i. Must have received Rituximab or another CD 20 antibody with one chemotherapy regimen appropriate for this disease (bendamustine or cytarabine, or anthracycline based treatment) and have ONE of the following:
• Relapsed disease after two lines of cytotoxic chemotherapy including administration of anti-CD20 antibody.
• Progressive disease after ≥second line BTK inhibitor.
• Relapse post-autologous transplant.
• Relapse post-allogeneic transplant.

You may not qualify if:

• Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential or plan to become pregnant during the study or within 1 month of the last dose of study treatment and women who are current lactating or plan to breastfeed during the study or within 1 week of the last dose of study treatment.
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
• HBV: Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before randomization. Patients who are hepatitis B PCR positive will be excluded.
• Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA positive will be excluded.
• Known active cytomegalovirus (CMV) infection (Unknown or negative status are eligible).
• History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon requiring steroid therapy defined as \>20 mg of prednisone or equivalent daily.
• Presence of ≥ grade 3 non-hematologic toxicities as per CTCAE version 5.0 from any previous treatment unless it is felt to be due to underlying disease.
• Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution. Minimum of 14 days or 5 half-lives of the drug (whichever is shorter) washout prior to apheresis.
• Refusal to participate in the long-term follow-up protocol.
• Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.
• Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment and a remission documented within 8 weeks of planned CAR-T cell infusion by MRI brain and CSF analysis.
• Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are excluded if they are \<100 days post-transplant, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.
• Prior allogeneic CAR T-cell therapy \<100 days from prior CAR T-cell treatment.
• Previous recipients of autologous CAR-T cell therapy directed at either cluster of differentiation 19 (CD19) or CD20 are excluded if they are \<100 days post prior CAR-T cell treatment (does not include re-enrollment) or have \>5% residual circulating CAR-T as measured by flow cytometry using a CD19 CAR detection reagent (Miltenyi Biotec).
• a. Patients with prior CAR-T treatment against CD19 or CD20 must have repeat biopsy post-CAR-T cell therapy confirming a minimum of 5% CD19 or CD20 positivity by immunohistochemistry or flow cytometry.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Burkitt Lymphoma

Interventions

pirtobrutinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Nirav Shah, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: August 14, 2023
• Study Start: February 6, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)