Study of Welgenaleucel (UWC19) in Patients With Relapsed or Refractory B-cell Lymphoma

Study Overview
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Brief Summary
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This is an open-label, single-center Phase 1/2 study with a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2) in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

Official Title
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Phase 1 Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of Welgenaleucel (UWC19) in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Conditions
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B-cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Genetic: Welgenaleucel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a primary diagnosis of B cell non-Hodgkin lymphoma - Histologically confirmed: Diffuse Large B Cell Lymphoma (DLBCL), Primary Mediastinal Large B Cell Lymphoma (PMBCL), Transformation Follicular Lymphoma (TFL), High grade B-cell Lymphoma (HGBCL), Mantle cell Lymphoma (MANT), Burkitt Lymphoma (BURK), Lymphoblastic Lymphoma Chemotherapy-refractory disease, defined as one of more of the following No response to last line of therapy OR Refractory post-autologous stem cell transplant (ASCT) Individuals must have received adequate prior therapy including at a minimum: anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and an anthracycline containing chemotherapy regimen for individual with transformed FL must have chemorefractory disease after transformation to DLBCL. No active infection of HIV, HTLV and Syphilis Adequate renal function Adequate hepatic function Adequate cardiac function Adequate venous access for apheresis, and no other contraindications for leukapheresis Voluntary informed consent is given. Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: Received allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) Body weight less than 30 kg Pregnant or lactating women. Uncontrolled active infection. History of hepatitis B or hepatitis C infection. Previously treatment with any gene therapy products or cell therapy product in past 28 days. HIV infection. Lymphoma with central nervous system (CNS) involvement Have autoimmune disorders Have active infection or inflammatory disorders Prescreening test results in expansion rate less than 5 folds An allergy to gentamycin and/or streptomycin

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A standard 3+3 trial design will be used Welgenaleucel(UWC19) dose escalation cohorts. The planned dose escalation cohort levels for Welgenaleucel (UWC19) are 4, 8, 12, 16 and 20 x10^6 CAR-T cells/kg.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Welgenaleucel (UWC19)<br>Part I The safety and efficacy of Welgenaleucel (UWC19) will be evaluated in a standard 3+3 dose escalation approach.The planned dose escalation cohort levels for Welgenaleucel (UWC19) are 4, 8, 12, 16 and 20 x10^6 CAR-T cells/kg administered intravenously once. | Genetic: Welgenaleucel<br>* Welgenaleucel (UWC19) is a CD19-directed immunotherapy consisting of autologous T cells, which is reprogrammed to target cells that express CD19.<br>* Other names: UWC19;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | A standard 3+3 trial design will be used for Welgenaleucel (UWC19) dose escalation cohorts.The dosing of Welgenaleucel (UWC19) will be divided into 5 cohorts, the subjects will receive Welgenaleucel (UWC19) once on day 14-18 after apheresis. | 30 days after infusion | 
| Dose Limiting Toxicities (DLT) | The 3+3 design entails that if one patient out of the first three patients has a DLT, up to three additional patients will be entered at that dose level. | 30 days after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19, non-Hodgkin lymphoma, CAR-T cells