IRB Study Number 20-126
Status Recruiting
Phase Phase 3
Institutes Taussig Cancer Institute, Pediatric Institute
Description
Primary Objective
To determine the clinical benefit of tabelecleucel in subjects with EBV+ PTLD following (1) SOT and after failure of rituximab (Subgroup A) and rituximab plus chemotherapy (Subgroup B) or (2) allogeneic HCT after failure of rituximab, as measured by the objective response rate (ORR).
Secondary Objectives
To evaluate duration of response (DOR) in the SOT and HCT cohorts separately
To evaluate ORR and DOR in the SOT and HCT cohorts combined
To evaluate rates of CR and PR
To evaluate time to response and time to best response
To evaluate OS
To evaluate graft status (SOT subjects only)
To characterize the safety profile of tabelecleucel in this subject population
Inclusion Criteria
Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort)
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 [9] 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 CNS disease, a head diagnostic 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 (SOT subgroup A or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT subgroup B) for treatment of PTLD. Treatment failure is defined based on rituximab response as follows:
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
Failure to achieve a 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
Relapse/progression of PTLD after a response to rituximab (SOT subgroup A or HCT cohort) or rituximab plus chemotherapy (SOT subgroup B), 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
Males and females of any age
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 for subjects aged > 16 years; Lansky score ≥ 20 for subjects from birth to 16 years (performance status scales are included in Section 15.2)
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
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 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)
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and total bilirubin (TBILI) each < 5 × upper limit of normal (ULN); however, ALT, AST, and TBILI each ≤ 10 × ULN 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 (eg, elevated prothrombin time due to liver dysfunction, signs/symptoms of liver dysfunction such as asterixis, or similar).
- 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 CNSdirected 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 GvHD per the Center for International Blood and Marrow Transplant Research (CIBMTR) 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 HCT cohort only: 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 EBV-CTLs or CAR T-cells directed against B cells within 8 weeks of enrollment (SOT or HCT cohorts); or unselected DLI within 8 weeks of enrollment (HCT cohort 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
