UCART20x22: Allogeneic engineered T-cells expressing anti-CD20 and anti-CD22 Chimeric Antigen Receptors given following a lymphodepletion regimen
CLLS52: A monoclonal antibody that recognizes a CD52 antigen
Study summary
First-in-human, open-label, dose-finding and dose-expansion study of UCART20x22 administered intravenously in subjects with relapsed or refractory B-Cell Non-Hodgkin Lymphoma (B-NHL). The purpose of this study is to evaluate the safety and clinical activity of UCART20x22 and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Relapsed or refractory (R/R) mature B-NHL per 2016 WHO criteria and positive for CD20 and/or CD22
* Subjects with NHL subtypes defined by WHO:
* Dose-Finding Part: R/R mature B-NHL (except chronic lymphocytic leukemia/small lymphocytic leukemia \[CLL/SLL\], Richter's transformation from prior CLL/SLL, Burkitt's lymphoma, and Waldenstrom's macroglobulinemia)
* Dose-Expansion Part: R/R LBCL, defined as:
i. DLBCL; ii. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; iii. Transformed FL or transformed marginal zone lymphoma (MZL); iv. Follicular lymphoma Grade 3B
* R/R disease after at least 2 lines of prior treatment, which must have included:
* An Anti-CD20 MoAb and an anthracycline for DLBCL, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, primary mediastinal large B-cell lymphoma (PMBCL), or transformed FL or MZL
* An alkylating agent in combination with an anti-CD20 MoAb for FL
* An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton's tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL)
* Autologous anti-CD19 CAR T-cell therapy, if approved and available for the indicated lymphoma subtype, unless the subject is unable or is ineligible to receive approved autologous anti-CD19 CAR T-cell therapy (e.g., fail leukapheresis or manufacture, unable to wait for manufacture, CD19 negative disease, etc.)
* Autologous hematopoietic stem cells must be available prior to the start of the LD regimen if the subject is considered high-risk for prolonged hematologic toxicity.
Exclusion Criteria:
* Prior use of an investigational product (except for cell or gene therapies and MoAbs) within 5 half-lives or within 14 days, whichever is shorter, prior to start of LD regimen
* Previous approved therapy including chemotherapy, biologic (except MoAbs), or targeted therapy for R/R B-NHL with 5 half-lives or within 14 days, whichever is shorter, prior to start of the LD regimen
* \> 4 lines of therapy R/R B-NHL prior to start of the LD regimen.
* Prior MoAb therapy (approved or investigational) within 30 days prior to start of LD
* Prior systemic immunostimulatory agent within 3 half-lives prior to start of the LD regimen
* Prior cell or gene therapy (approved or investigational) within 6 months of the start of LD
* Prior cell or gene therapy (approved or investigational) targeting both CD20 and CD22
* Autologous HSCT infusion within 6 weeks of the start of LD
* Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD
* Active acute or chronic graft versus host disease (GvHD). Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD
* Radiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of LD regimen)
* Evidence of active central nervous system (CNS) lymphoma or previous CNS involvement of R/R B-NHL
* Presence of an active and clinically relevant CNS disorder
* Daily treatment with \>20 mg prednisone or equivalent
* Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens
* History of hypersensitivity to alemtuzumab
* History of neutralizing anti-drug antibody against alemtuzumab
* Any known uncontrolled cardiovascular disease within 3 months of enrollment
* Subjects requiring immunosuppressive treatment
* Major surgery within 28 days prior to start of LD
* Evidence of another uncontrolled malignancy within 2 years prior to Screening (except in situ nonmelanoma skin cell cancers and/or carcinoma in-situ of the cervix)
Primary outcome measure(s)
Dose finding and expansion parts: Incidence of adverse events/serious adverse events/dose limiting toxicity [Safety and Tolerability] — From study entry through month 12 Incidence, nature and severity of adverse events and serious adverse events in relation to UCART20x22 and/or lymphodepletion
Dose finding part: Occurrence of Dose Limiting Toxicities (DLTs) — Up to Day 28 post UCART20x22 infusion
Trial sites (10)
Facility
City
Region
Status
The University of Chicago Medical Center (UCMC)
Chicago
Illinois
Recruiting
Harvard Medical School - Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Rutgers Cancer Institute of New Jersey (CINJ) - New Brunswick
New Brunswick
New Jersey
Recruiting
Sarah Cannon - St. David South Austin Medical Center
Austin
Texas
Recruiting
Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
Pierre-Bénite
Auvergne Rhone Alpe
Recruiting
Centre Hospitalier Universitaire de Montpellier (CHU Montpellier) - Hopital Saint-Eloi
Montpellier
Occitanie
Recruiting
Centre Hospitalier Universitaire de Nantes (CHU de Nantes)-Hotel-Dieu
Nantes
France
Recruiting
Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Saint-Louis - Centre Integre en Cancerologie
Paris
Île-de-France Region
Recruiting
Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona
Pamplona
Navarre
Recruiting
Hospital Universitario Virgen del Rocio (HUVR) - Instituto de Biomedicina de Sevilla (IBIS)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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