Cellular Immunotherapy for Viral Induced Cancer - EBV Positive Lymphomas

Study Overview
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Brief Summary
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To investigate the efficacy of autologous Epstein-barr virus (EBV)-specific T cells for the treatment of EBV positive Diffuse Large B Cell Lymphoma (DLBCL), Hodgkin Lymphoma (HL) and Post-transplant Lymphoproliferative Disease (PTLD) after failing first line treatment.

Official Title
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A Phase 2 Open Label Study to Investigate the Safety and Clinical Activity of Autologous EBV-specific T Cells (CMD-003) for the Treatment of Patients With EBV Positive Lymphomas

Conditions
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Hodgkin Lymphoma, Lymphoma, Large B-Cell, Diffuse, Post-transplant Lymphoproliferative Disorder

Intervention / Treatment
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* Biological: baltaleucel-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study will include three primary cohorts, with any of the following EBV+ diseases: Cohort A - DLBCL, 1) in first or subsequent relapse, not eligible for autologous transplantation following salvage therapy OR 2) relapse following autologous transplantation. Cohort B - HL, brentuximab vedotin (BV) treatment failure or unable to tolerate BV. Cohort C - PTLD, rituximab treatment failure. Presence of active lymphoma or active PTLD, based on imaging performed within the previous 3 months. Tumor positive for EBV encoded RNA (EBER) based on report from certified laboratory. Absolute lymphocyte count (ALC) >500/µL Male or female ≥ 12 years of age Weight ≥ 35 kg Eastern Cooperative Oncology Group (ECOG) performance score 0-2, inclusively or Lansky score ≥ 60, as age appropriate Able to understand and comply with the requirements of the study and to provide written informed consent or age appropriate assent for pediatric patients. Exclusion Criteria: Known central nervous system (CNS) lymphoma Primary refractory HL or DLBCL Bulky disease Relapse or progression following previous autologous EBV specific T cell treatment. Use of systemic corticosteroids > 0.5 mg/kg/day prednisolone or equivalent does of alternative corticosteroid within 10 days prior to obtaining 200 mL starting material Positive for HIV, hepatitis B, hepatitis C, syphilis or human T cell leukemia virus (HTLV). Patient is pregnant or lactating Systemic fungal, bacterial, viral or other infection that is not controlled Prior allogeneic hematopoietic stem cell transplantation (allo HSCT) Known history of primary immunodeficiency

Ages Eligible for Study
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Minimum Age: 12 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: baltaleucel-T<br>Treatment consist of up to 5 doses of 2x10E7 cells/m2 administered intravenously every 2 weeks. | Biological: baltaleucel-T<br>* Autologous EBV-specific T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | Best single observed response, complete response (CR) or partial response (PR) per Lugano 2014 Disease Response Criteria, during 12 month follow-up. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Adverse events will be recorded from the time of the first investigational cell product dose is administered until 30 days after the last administration. Serious events recorded for up to 1 year after administration. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, Epstein-Barr Virus, PTLD, EBV, CIVIC, HL, T cell