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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

PHASE3RECRUITING

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 (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

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Study details:

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-R and SOT-R+C (Cohort \[C\]-SOT) or HCT after failure of rituximab (C-HCT). SOT-R further included participants:. 1.

who did not receive chemotherapy and did not have a documented medical reason not to receive chemotherapy (SOT-Ro) or. 2. who were considered chemotherapy ineligible/inappropriate (SOT-R-Ci).

Combined population (SOT-R-Ci, SOT-R+C, and HCT) and (SOT-R-Ci and SOT-R+C) who received commercial product, or a product manufactured using a comparable process version (PV) were also used for analysis of outcomes. 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 (C-SOT) or up to 4 different HLA restrictions (C-HCT).

The study includes a total of 5 years of follow-up for disease and survival status.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

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

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

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

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.

Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.

Males and females of any age.

Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects < 16 years

For C-HCT 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

Adequate organ function

Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support

Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, 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)

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

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

Exclusion criteria

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

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

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.

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

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

For C-HCT: active adenovirus viremia

Need for vasopressor or ventilatory support

Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment

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

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

Inability to comply with study-related procedures

Any medical condition or organ system dysfunction that in the investigator's opinion, could compromise the participant's safety or ability to complete the study

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Eligibility

Age eligible for study : 0 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2017-12-29

Primary completion: 2025-08-01

Study completion finish: 2027-06-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT03394365

Intervention or treatment

BIOLOGICAL: tabelecleucel

Conditions

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

Image related to Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)

Condition: Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications and more
BIOLOGICAL: tabelecleucel
Westmead, New South Wales, Australia and more
Sponsor: Atara Biotherapeutics

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Find a site

Closest Location:

The Children's Hospital at Westmead (Pediatrics only)

Research sites nearby

Select from list below to view details:

The Children's Hospital at Westmead (Pediatrics only)
Westmead, New South Wales, Australia
Westmead Hospital (Adults only)
Westmead, New South Wales, Australia
The Prince Charles Hospital (Adults only)
Chermside, Queensland, Australia
Royal Adelaide Hospital (Adults only)
Adelaide, South Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Cohort SOT-R (C-SOT-R) Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel.	BIOLOGICAL: tabelecleucel Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
EXPERIMENTAL: Cohort SOT-R+C (C-SOT-R+C) Participants with EBV+ PTLD following SOT that has failed both rituximab and chemotherapy will receive IV tabelecleucel.	BIOLOGICAL: tabelecleucel Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
EXPERIMENTAL: Cohort HCT (C-HCT) Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen will receive IV tabelecleucel.	BIOLOGICAL: tabelecleucel Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Objective response rate (ORR) in the Analysis Cohorts C-SOT, C-HCT, and Combined Population (C-SOT-R+C, C-SOT-R-Ci, and C-HCT) Who Received Commercial Product, or a Product Manufactured Using a Comparable PV	Not Specified	2 years

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Duration of response (DOR) in the Analysis Cohorts C-SOT and C-HCT Separately	Not Specified	2 years
ORR and DOR in the Analysis Cohorts C-SOT and C-HCT Combined	Not Specified	2 years
ORR and DOR in Participants who Received Commercial Product or a Product Manufactured Using a Comparable PV in the Analysis Cohorts C-SOT-R-Ci and C-SOT-R+C Separately and Combined, and in the Analysis Cohort C-HCT	Not Specified	2 years
DOR in the Analysis Cohort of the Combined Population (C-SOT-R+C, C-SOT-R-Ci, and C-HCT) who Received Commercial Product or a Product Manufactured Using a Comparable PV	Not Specified	2 years
Rates of Complete Response (CR) and Partial Response (PR)	Not Specified	2 years
Time to Response	Not Specified	2 years
Time to Best Response	Not Specified	2 years
Overall Survival (OS)	Not Specified	2 years
Rates of Allograft Loss or Rejection Episodes (Analysis Cohort C-SOT)	Not Specified	2 years

Frequently Asked Questions

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References

Clinical Trials Gov: 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