A study for subjects after organ or cell transplantation after failure of prior treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pierre Fabre Medicament

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 May 2020 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pierre Fabre Medicament

External identifiers

EU CT number

2024-516622-57-00

EudraCT number

2017-002949-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Safety, Pharmacodynamic

To determine the clinical benefit of tabelecleucel (ATA129; allogeneic Epstein-Barr virus specific cytotoxic T lymphocytes [EBV-CTLs]) as measured by the objective response rate (ORR) in participants with EBV associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the following analysis cohorts (1) solid organ transplant (SOT) after failure of the following: a) rituximab (SOT-R), which includes participants who did not receive chemotherapy and did not have a documented medical reason not to receive chemotherapy (SOT-Ro); or who were considered chemotherapy ineligible/inappropriate (SOT-R-Ci). b) rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab or (3) A combined population of SOT-R-Ci, SOT-R+C, and HCT who received commercial product or a product manufactured using a comparable process version (PV).

Secondary objectives 9

1. To evaluate duration of response (DOR) in the SOT and HCT cohorts separately
2. To evaluate ORR and DOR in the SOT and HCT cohorts combined
3. To evaluate ORR and DOR in subjects who received commercial product or a product manufactured using a comparable PV in the following: SOTR-Ci and SOT-R+C combined, and separately, HCT
4. To evaluate DOR in a combined population (SOT-R-Ci, SOT-R+C, and HCT) who received commercial product or a product manufactured using a comparable PV
5. To evaluate rates of complete response (CR) and partial response (PR)
6. To evaluate time to response and time to best response
7. To evaluate overall survival (OS)
8. To evaluate graft status (SOT participants only)
9. To characterize the safety profile of tabelecleucel in this participant population

Conditions and MedDRA coding

Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002025-PIP04-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 -diagnostic computed tomography, except when contraindicated or mandated by local practice, then magnetic resonance imaging may be used. For Participants with treated central nervous system (CNS) disease, head diagnostic computed tomography and/or brain/spinal magnetic resonance imaging 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-R or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT-R+C) for treatment of PTLD. Treatment failure is defined based on rituximab response as follows: a. Radiographic disease progression per Lugano Classification following a minimum cumulative dose of 1125 mg/m2 rituximab (typically, 3 weekly doses of 375 mg/m2), or b. Failure to achieve CR or PR, defined by Lugano radiographic criteria, after a minimum cumulative dose of 1500 mg/m2 rituximab (typically, 4 weekly doses of 375 mg/m2), or c. Relapse/progression of PTLD after a response to rituximab (SOT-R or HCT cohort) or rituximab plus chemotherapy (SOT-R+C), defined as radiographic and/or biopsy evidence of relapse/progression consistent with PTLD; if the underlying disease for which the subject underwent allogeneic HCT (HCT cohort) was lymphoma, biopsy confirmation of relapsed EBV+ PTLD is required.
6. Males and females of any age.
7. Eastern Cooperative Oncology Group performance status ≤ 3 for Participants aged ≥ 16 years; Lansky score ≥ 20 for Participants < 16 years.
8. 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 participant underwent transplant must be in morphologic remission.
9. Adequate organ function: a. Absolute neutrophil count ≥ 1000/μL (SOT cohort) or ≥ 500/μL (HCT cohort), with or without cytokine support b. 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 participant 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, version 5.0) c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each < 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × the 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 (e.g., elevated prothrombin time due to liver dysfunction, signs/symptoms of liver dysfunction such as asterixis, or similar).
10. Participant or participant's representative is willing and able to provide written informed consent.

Exclusion criteria 12

1. Currently active Burkitt, T cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.
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 participant is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE: Participants with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
4. Suspected or confirmed grade ≥ 2 graft-versus-host disease 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 only: 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 EBV-CTLs 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
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR (CR or PR) obtained following administration of tabelecleucel with up to 2 different HLA restrictions in each of the following analysis cohorts: • SOT • HCT • A combined population (SOT-R-Ci, SOT-R+C, and HCT) following administration of commercial product or a product manufactured using a comparable PV

Secondary endpoints 8

1. DOR in the SOT and HCT cohorts separately.
2. ORR and DOR in SOT and HCT cohorts combined.
3. ORR and DOR in subjects who received commercial product or a product manufactured using a comparable PV in the following: SOT-R-Ci and SOT-R+C combined, and separately, HCT
4. DOR in a combined population (SOT-R-Ci, SOT-R+C, and HCT) who received commercial product or a product manufactured using a comparable PV
5. Rates of CR and PR
6. Time to response and time to best response
7. OS
8. Rates of allograft loss/rejection episodes (for SOT cohort only)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pierre Fabre Medicament

Sponsor organisation

Pierre Fabre Medicament

Address

Les Cauquillous

City

Lavaur

Postcode

81500

Country

France

Scientific contact point

Organisation

Pierre Fabre Medicament

Contact name

Pierre Fabre Medicament

Public contact point

Organisation

Pierre Fabre Medicament

Contact name

Pierre Fabre Medicament

Third parties 7

Sponsor responsibilities

Article 77 compliance

Pierre Fabre Medicament

Contact point sponsor

Pierre Fabre Medicament

Article 77 implementation

Pierre Fabre Medicament

Locations

5 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications