Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

Stem Cell Transplant Complications Clinical Trial

— ALLELE  

Official title:

Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03394365
• Other study ID #: ATA129-EBV-302
• Status: Recruiting
• Phase: Phase 3
• Start date: December 29, 2017
• Est. completion date: June 2027

Study information

• Verified date: June 2022
• Source: Atara Biotherapeutics
• Contact: Aditi Mehta, DO
• Phone: 650-278-8930
• Email: clinicalstudies[@]atarabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Description:

This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of rituximab and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab (HCT cohort).

Enrollment will be preceded by confirmation of availability of partially human leukocyte antigen (HLA) matched and restricted tabelecleucel for the participant.

Study procedures and product administration will be the same for each cohort. Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, participants will receive intravenous tabelecleucel at a dose of 2×10^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35. Treatment will continue until maximal response, unacceptable toxicity, initiation of non protocol therapy, or failure of tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT cohort). The study includes a total of 5 years of follow-up for disease and survival status.

This protocol has been amended to include the HCT cohort from clinical study ATA129-EBV-301 (NCT03392142).

NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status "active, not recruiting" due to COVID-19 restrictions.

Other known NCT identifiers

• NCT03392142

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: June 2027
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort)

2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD

3. Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor

4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score = 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used.For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.

5. Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (SOT subgroup A or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT subgroup B) for treatment of PTLD.

6. Eastern Cooperative Oncology Group performance status = 3 for subjects aged = 16 years; Lansky score = 20 for subjects < 16 years

7. For HCT cohort only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the subject underwent transplant must be in morphologic remission

8. Adequate organ function

1. Absolute neutrophil count = 1000/µL, (SOT cohort) or = 500/µL (HCT cohort), with or without cytokine support

2. Platelet count = 50,000/µL, with or without transfusion or cytokine support. For HCT cohort, platelet count < 50,000/µL but = 20,000/µL, with or without transfusion support, is permissible if the subject has not had grade = 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events [CTCAE], version 5.0)

3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each < 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each = 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction

9. Subject or subject's representative is willing and able to provide written informed consent

Exclusion Criteria:

1. Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma

2. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis

3. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.

4. Suspected or confirmed grade = 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment

5. Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment

6. For HCT cohort: active adenovirus viremia

7. Need for vasopressor or ventilatory support

8. Antithymocyte globulin or similar anti-T cell antibody therapy = 4 weeks prior to enrollment

9. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (SOT or HCT cohorts), or unselected donor lymphocyte infusion within 8 weeks of enrollment (HCT cohort only)

10. Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception

11. Inability to comply with study-related procedures

Related Conditions & MeSH terms

• Allogeneic Hematopoietic Cell Transplant
• Epstein-Barr Virus Infections
• Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)
• Lymphoproliferative Disorders
• Solid Organ Transplant Complications
• Stem Cell Transplant Complications

Intervention

Biological:
• tabelecleucel
Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital (Adults only)	Adelaide	South Australia
Australia	The Prince Charles Hospital (Adults only)	Chermside	Queensland
Australia	The Royal Children's Hospital Melbourne (Pediatrics only)	Melbourne	Victoria
Australia	Fiona Stanley Hospital (Adults only)	Murdoch	Western Australia
Australia	The Children's Hospital at Westmead (Pediatrics only)	Westmead	New South Wales
Australia	Westmead Hospital (Adults only)	Westmead	New South Wales
Austria	Medizinische Universitat Wien (Adults only)	Wien
Belgium	Universitair Ziekenhuis Leuven (Adults and Pediatrics)	Leuven	Flemish Brabant
Belgium	Centre Hospitalier Universitaire de Liège Site Sart Tilman (Adults and Pediatrics)	Liège	Brussels
Canada	Alberta Children's Hospital (Adults and Pediatrics)	Calgary	Alberta
Canada	Princess Margaret Cancer Centre (Adults only)	Toronto	Ontario
Canada	Sick Kids (Pediatrics only)	Toronto	Ontario
France	Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)	Lille cedex	Nord-Pas-de-Calais
France	Hôpital Saint Antoine (Adults only)	Paris	Ile-de-France
France	Hôpital Necker-Enfants Malades (Pediatrics only)	Paris 15	Île-de-France
France	Hôpital Universitaire Pitié Salpêtrière (Adults only)	Paris Cedex 13	Île-de-France
France	Groupe Hospitalier du Haut Leveque (Adults only)	Pessac	Aquitaine
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (Adults only)	Milano
Italy	Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)	Pavia
Italy	Fondazione Policlinico Universitario Agostino Gemelli (Adults only)	Roma
Italy	Ospedale Pediatrico Bambino Gesu (Pediatrics only)	Roma
Italy	Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Adults only)	Torino
Spain	Hospital Duran i Reynals	Badalona	Barcelona
Spain	Hospital Universitari Vall d'Hebrón - Institut de Recerca (Adults and Pediatrics)	Barcelona
Spain	Hospital General Universitario Gregorio Marañón (Adults and Pediatrics)	Madrid
Spain	Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics)	Santander	Cantabria
Spain	University Hospital Virgen del Rocio (Adults and Pediatrics)	Sevilla
Spain	Hospital Universitario La Fe (Adults and Pediatrics)	Valencia
United Kingdom	University Hospitals Birmingham NHS Foundation Trust (Adults only)	Birmingham	England
United Kingdom	Imperial College Healthcare NHS Trust (Adults only)	London	England
United Kingdom	King's College Hospital NHS Foundation Trust (Adults only)	London	England
United States	Children's Healthcare of Atlanta at Egleston (Pediatrics)	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University (Adults only)	Atlanta	Georgia
United States	University of Maryland School of Medicine (Adults only)	Baltimore	Maryland
United States	Dana Farber Cancer Institute, Brigham and Women's Hospital (Adults and Pediatrics)	Boston	Massachusetts
United States	Montefiore Medical Center (Adults only)	Bronx	New York
United States	Montefiore Medical Center (Pediatrics only)	Bronx	New York
United States	University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center (Adults and Pediatrics)	Chapel Hill	North Carolina
United States	Medical University of South Carolina (Adults and Pediatrics)	Charleston	South Carolina
United States	Carolinas Medical Center/Levine Children's Hospital (Adults and Pediatrics)	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago (Adults and Pediatrics)	Chicago	Illinois
United States	University of Chicago Medical Center - Duchossois Center for Advanced Medicine (Adults only)	Chicago	Illinois
United States	Cleveland Clinic Foundation (Adults and Pediatrics)	Cleveland	Ohio
United States	Nationwide Children's Hospital (Pediatrics only)	Columbus	Ohio
United States	The Ohio State University - Arthur G. James Cancer Center Hospital (Adults and Pediatrics)	Columbus	Ohio
United States	Baylor Scott and White Research Institute (Adults only)	Dallas	Texas
United States	University of Texas Southwestern Medical Center - Children's Medical Center (Pediatrics only)	Dallas	Texas
United States	City of Hope (Adults and Pediatrics)	Duarte	California
United States	Duke Cancer Institute (Adults only)	Durham	North Carolina
United States	University of Florida (Adults and Pediatrics)	Gainesville	Florida
United States	MD Anderson Cancer Center (Adults and Pediatrics)	Houston	Texas
United States	University of California San Diego Moores Cancer Center (Adults only)	La Jolla	California
United States	Loma Linda University Cancer Center (Adults only)	Loma Linda	California
United States	Children's Hospital Los Angeles, Div. of Research Immunology/BMT (Adults and Pediatrics)	Los Angeles	California
United States	UCLA Medical Center (Adults and Pediatrics)	Los Angeles	California
United States	Loyola University Medical Center (Adults and Pediatrics)	Maywood	Illinois
United States	Saint Jude Children's Research Hospital (Pediatrics only)	Memphis	Tennessee
United States	University of Miami/Jackson Memorial Hospital (Adults only)	Miami	Florida
United States	Froedtert Hospital & the Medical College of Wisconsin (Adults only)	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center Henry-Joyce Cancer Clinic (Adults and Pediatrics)	Nashville	Tennessee
United States	Yale University (Adults and Pediatrics)	New Haven	Connecticut
United States	Columbia University Medical Center (Adults and Pediatrics)	New York	New York
United States	Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)	New York	New York
United States	Weill Cornell Medicine (Adults only)	New York	New York
United States	Children's Hospital of Philadelphia (Pediatrics only)	Philadelphia	Pennsylvania
United States	University of Pennsylvania (Adults only)	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center (Adults only)	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University Physicians Pavilion (Adults and Pediatrics)	Portland	Oregon
United States	University of California Davis Comprehensive Cancer Center (Adults only)	Sacramento	California
United States	Washington University School of Medicine (Adults only)	Saint Louis	Missouri
United States	MedStar Georgetown University Hospital (Adults and Pediatrics)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Atara Biotherapeutics

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR) in the SOT or HCT cohort		2 years
Secondary	Duration of response (DOR) in SOT and HCT cohorts separately		2 years
Secondary	ORR and DOR in SOT and HCT cohorts combined		2 years
Secondary	Rates of complete response (CR) and partial response (PR)		2 years
Secondary	Time to response		2 years
Secondary	Time to best response		2 years
Secondary	Overall survival (OS)		2 years
Secondary	Rates of allograft loss or rejection episodes (SOT cohort)		2 years