CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell Malignancies
Phase I/II Study of Tandem, Bispecific Anti-CD19 Anti-CD20 CAR-T Cells for Patients With Relapsed and/or Refractory B Cell Malignancies
1 other identifier
interventional
100
1 country
1
Brief Summary
This is a Phase I/II, interventional, single-arm, open-label, treatment study designed to evaluate the safety and efficacy of Interleukin-7 and Interleukin-15 (IL-7/IL-15) manufactured chimeric antigen receptor (CAR)-20/19-T cells as well as the feasibility of a flexible manufacturing schema in adult patients with B cell malignancies that have failed prior therapies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 2, 2019
CompletedFirst Posted
Study publicly available on registry
December 4, 2019
CompletedStudy Start
First participant enrolled
May 18, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 28, 2029
February 23, 2026
February 1, 2026
6.8 years
December 2, 2019
February 19, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Adverse Events after CAR 20/19-T cell infusion
Incidence of adverse events using NCI CTCAE version 5.0.
Within the first 28 days after infusion
Study Arms (6)
8/12 Day Production of CAR-T for NHL
EXPERIMENTALPhase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with relapsed, refractory B-cell NHL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts at eight or 12-day manufacturing. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 in each group.
8/12 Day Production of CAR-T for CLL
EXPERIMENTALPhase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: The enrollment will cap at 24 subjects.
8/12 Flexible Manufacturing with Mandated Cryopreservation
EXPERIMENTAL8/12 flexible manufacturing with mandated cryopreservation prior to infusion of LV20.19 CAR T-cells. The enrollment will cap at 24 subjects.
12-Day Production of Car-T Cells for NHL
EXPERIMENTALPhase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with relapsed, refractory B-cell NHL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts at 12-day manufacturing. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 in each group.
8/12 Day Production of CAR-T for Relapsed/Refractory Primary or Secondary CNS Lymphoma
EXPERIMENTALPhase 1: Determine safety of 2.5x106 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with primary/secondary central nervous system (CNS) lymphoma. Phase 1b: Safety and efficacy will be evaluated in this study that will enroll 12 to 24 patients.
Phase 2 - Efficacy of CAR-20/19-T cells in MCL
EXPERIMENTALSingle-stage Phase II design with three-month CR as the target endpoint.
Interventions
A fixed dose of 2.5 x 10\^6 CAR-20/19-T cells/kg expanded with IL-7/IL-15.
A fixed cryopreserved dose of 2.5 x 10\^6 CAR-20/19-T cells/kg expanded with IL-7/IL-15.
A fixed dose of 2.5 x 10\^6 CAR-20/19-T cells/kg expanded with IL-7/IL-15.
Eligibility Criteria
You may qualify if:
- Patients must be aged ≥18 years and ≤80 years with relapsed or refractory B-cell non-Hodgkin Lymphoma.
- Absolute cluster of differentiation 3 (CD3) count ≥50 mm\^3.
- Magnetic resonance imaging (MRI) brain and lumbar puncture with cerebrospinal fluid (CSF) analysis by cytology and flow cytometry without evidence of central nervous system (CNS) involvement ONLY in patients with history of CNS involvement or clinical suspicion at the time of enrollment EXCEPT Arm E subjects.
- Measurable disease must be documented within four weeks of the time of consent defined as nodal lesions greater than 15 mm in the long axis or extranodal lesions \>10 mm in long and short axis OR bone marrow involvement that is biopsy proven for B-cell NHL (see separate criteria for CLL and primary/secondary CNS lymphoma).
- Karnofsky performance score ≥70.
- Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<5 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<5 x ULN, or considered not clinically significant as per the clinical PIs discretion (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.
- ANC≥1000 with no G-CSF within 72 hours or pegylated G-CSF within 14 days.
- Platelets≥50,000 with no transfusion within 72 hours.
- Adequate renal function, defined as creatinine clearance \>60 ml/min AND serum Cr≤1.5 mg/dL.
- a. No IV hydration within 24 hours of eligibility. b. No dialysis dependent renal failure within three months of planned CAR infusion.
- Able to provide written informed consent.
- Agree to practice birth control during the study.
- Adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of ≥45% (by cardiac echocardiogram (ECHO) or multigated acquisition scan (MUGA)) and adequate pulmonary function as indicated by room air oxygen saturation of ≥92%.
- Expected survival \>12 weeks.
- Negative urine or serum pregnancy test in females of child bearing potential at study entry.
- +49 more criteria
You may not qualify if:
- Positive beta- human chorionic gonadotropin (HCG) in female of childbearing potential.
- Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
- 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 (Not applicable to Arm E cohort.)
- a. 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
- Previous recipients of autologous CAR-T cell therapy directed at either 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
- Anti-CD20 antibody treatment within 4 weeks of cell infusion
- Anti-CD19 antibody treatment within 4 weeks of cell infusion
- Cytotoxic chemotherapy other than lymphodepletion within 14 days of CAR-T cell infusion
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Medical College of Wisconsin and Froedtert Hospital
Milwaukee, Wisconsin, 53226, United States
Related Publications (2)
Shah NN, Colina AS, Johnson BD, Szabo A, Furqan F, Kearl T, Schneider D, Vargas-Cortes M, Schmeling JL, Dwinell MB, Palen K, Longo W, Hematti P, Zamora AE, Hari P, Bucklan D, Cunningham A, Hamadani M, Fenske TS. Phase I/II Study of Adaptive Manufactured Lentiviral Anti-CD20/Anti-CD19 Chimeric Antigen Receptor T Cells for Relapsed, Refractory Mantle Cell Lymphoma. J Clin Oncol. 2025 Jul 10;43(20):2285-2295. doi: 10.1200/JCO-24-02158. Epub 2025 Mar 31.
PMID: 40163793DERIVEDZurko JC, Xu H, Chaney K, Schneider D, Szabo A, Hari P, Johnson BD, Shah NN. Bispecific targeting of CD20 and CD19 increases polyfunctionality of chimeric antigen receptor T-cell products in B-cell malignancies. Cytotherapy. 2022 Aug;24(8):767-773. doi: 10.1016/j.jcyt.2022.03.011. Epub 2022 May 18.
PMID: 35597752DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nirav Shah, MD
Medical College of Wisconsin
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
December 2, 2019
First Posted
December 4, 2019
Study Start
May 18, 2020
Primary Completion (Estimated)
February 28, 2027
Study Completion (Estimated)
February 28, 2029
Last Updated
February 23, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share