RECRUITING

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

Conditions

Non Hodgkin Lymphoma Diffuse Large B Cell Lymphoma Follicular Lymphoma Marginal Zone Lymphoma Mantle Cell Lymphoma Burkitt Lymphoma CAR-T Chimeric antigen receptor T-cell therapy CAR Therapy Pirtobrutinib B Cells BTK inhibitor Bruton's tyrosine kinase

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase I Study of LV20.19 CAR T-cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies

Quick Facts

Study Start:2025-02-06

Study Completion:2027-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05990465

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 81 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	1. 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. 2. Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below: 1. 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. 2. 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. 3. Known active cytomegalovirus (CMV) infection (Unknown or negative status are eligible). 4. History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon requiring steroid therapy defined as \>20 mg of prednisone or equivalent daily. 5. 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. 6. 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. 7. Refusal to participate in the long-term follow-up protocol. 8. Patients with active CNS involvement by malignancy on MRI or by lumbar puncture. 1. 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. 9. 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. 10. Prior allogeneic CAR T-cell therapy \<100 days from prior CAR T-cell treatment. 11. 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). 12. Anti-CD20 antibody treatment within 4 weeks of cell infusion. 13. Anti-CD19 antibody treatment within 4 weeks of cell infusion. 14. Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than replacement dose steroids) within 7 days prior to apheresis collection for CAR-T cells. 15. No other oral chemotherapeutic agents or antibody directed treatment after starting pirtobrutinib other than steroids or radiation to a single site in a palliative fashion. 16. Patients post solid organ transplant who develop high grade lymphomas or leukemias. 17. Concurrent active malignancy other than basal or squamous cell carcinomas of the skin (underlying low-grade lymphoma chronic lymphocytic leukemia/Follicular lymphoma (FL) / Marginal zone lymphoma (MZL) is allowable in patients with transformed large cell lymphoma/Richter's. 18. Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor. 19. History of stroke or intracranial hemorrhage within 6 months of randomization. 20. Significant cardiovascular disease defined as myocardial infarction within 6 months of randomization, congestive heart failure with ejection fraction \<30%, active unstable angina, QT prolongation (QTcF)\>470 msec on ECG. 21. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug. 22. Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist. 23. Patients who had surgery within 4 weeks prior to randomization. 24. Patients who have received vaccination with live vaccine within 28 days prior to randomization. 25. Patients with known hypersensitivity to any of the excipients of pirtobrutinib.

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

1. 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.
2. Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
1. 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.
2. 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.
3. Known active cytomegalovirus (CMV) infection (Unknown or negative status are eligible).
4. History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon requiring steroid therapy defined as \>20 mg of prednisone or equivalent daily.
5. 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.
6. 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.
7. Refusal to participate in the long-term follow-up protocol.
8. Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.
1. 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.
9. 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.
10. Prior allogeneic CAR T-cell therapy \<100 days from prior CAR T-cell treatment.
11. 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).
12. Anti-CD20 antibody treatment within 4 weeks of cell infusion.
13. Anti-CD19 antibody treatment within 4 weeks of cell infusion.
14. Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than replacement dose steroids) within 7 days prior to apheresis collection for CAR-T cells.
15. No other oral chemotherapeutic agents or antibody directed treatment after starting pirtobrutinib other than steroids or radiation to a single site in a palliative fashion.
16. Patients post solid organ transplant who develop high grade lymphomas or leukemias.
17. Concurrent active malignancy other than basal or squamous cell carcinomas of the skin (underlying low-grade lymphoma chronic lymphocytic leukemia/Follicular lymphoma (FL) / Marginal zone lymphoma (MZL) is allowable in patients with transformed large cell lymphoma/Richter's.
18. Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor.
19. History of stroke or intracranial hemorrhage within 6 months of randomization.
20. Significant cardiovascular disease defined as myocardial infarction within 6 months of randomization, congestive heart failure with ejection fraction \<30%, active unstable angina, QT prolongation (QTcF)\>470 msec on ECG.
21. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug.
22. Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
23. Patients who had surgery within 4 weeks prior to randomization.
24. Patients who have received vaccination with live vaccine within 28 days prior to randomization.
25. Patients with known hypersensitivity to any of the excipients of pirtobrutinib.

Contacts and Locations

Study Contact

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505

cccto@mcw.edu

Principal Investigator

Nirav Shah, MD

PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Study Locations (Sites)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Medical College of Wisconsin

Nirav Shah, MD, PRINCIPAL_INVESTIGATOR, Medical College of Wisconsin

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-06

Study Completion Date2027-07

Study Record Updates

Study Start Date2025-02-06

Study Completion Date2027-07

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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