An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects with Epstein-Barr Virus-associated Diseases

ENROLLING
Protocol # :
21-114
Conditions
Epstein-Barr Virus (EBV)-Associated Diseases
EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (EBV+ PID LPD)
EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (EBV+ AID LPD)
EBV+ Posttransplant Lymphoproliferative Disease in Central Nervous System (EBV+ CNS PTLD)
EBV+ Post-transplant Lymphoproliferative Disease (EBV+ PTLD)
Solid Organ Transplant Complications
Lymphoproliferative Disorders
Allogeneic Hematopoietic Cell Transplant
Stem Cell Transplant Complications
EBV+ Sarcomas
Leiomyosarcoma
Phase
II
Disease Sites
Other Hematopoietic
Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Multiple Myeloma
Lymphoid Leukemia
Myeloid and Monocytic Leukemia
Leukemia, other
Principal Investigator
Nikiforow, Sarah
Site Research Nurses
Beshere, Gianna
Fontana, Brittney
Halloran, Elizabeth
More, Avnee, P.
Pasquale, Kathryn, Mary
Verrill, Kelly

Trial Description

The purpose of this study is to assess the efficacy and safety of tabelecleucel in
participants with Epstein-Barr virus (EBV) associated diseases.

Eligibility Requirements

Inclusion Criteria:

- Diagnosis of EBV+ disorder

- Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16
years; Lansky score >= 20 for participants from >=1 year to < 16 years

- Adequate organ function test results, unless organ dysfunction is considered to be due
to the underlying EBV-associated disease by the investigator

Cohort-specific Inclusion Criteria:

- For participants with PID LPD:

- R/R or newly diagnosed PID LPD for whom the standard first-line therapy is
inappropriate, as determined by investigator. The LPD is confirmed by at least
biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or
without radiographically measurable intracranial disease with EBV detected in
CSF.

- Participants with R/R disease must have had at least one prior line of systemic
therapy and one of the following: radiographic disease progression per Lugano
Classification (Cheson BD, et al. J Clin Oncol. 2014;27:3059) during or after
treatment or failure to achieve a CR or partial response (PR) (defined by Lugano
radiographic criteria) after standard first-line therapy

- Participant may have systemic disease only, systemic and CNS disease, or CNS
disease only

- For participants with AID LPD:

- R/R or newly diagnosed AID LPD for whom the standard first line therapy is
inappropriate, as determined by the investigator. The LPD is confirmed by at
least biopsy-proven EBV+ LPD or positive CSF cytology, with or without
radiographically measurable intracranial disease, with EBV detected in CSF.

- Participants with R/R disease must have had at least one prior line of systemic
therapy and one of the following: radiographic disease progression per Lugano
Classification during or after treatment or failure to achieve a CR or PR
(defined by Lugano radiographic criteria) after standard first-line therapy

- Participant may have systemic disease only, systemic and CNS disease, or CNS
disease only

- For participants with AID etiology or AID attributable to immunosenescence,
objective laboratory evidence of immunodeficiency

- For participants with CNS PTLD:

- R/R or newly diagnosed EBV+ CNS PTLD for whom the standard first-line therapy is
inappropriate, as determined by the investigator. The CNS PTLD is histologically
confirmed by at least biopsy-proven EBV+ CNS PTLD or positive CSF cytology with
or without radiographically measurable intracranial disease with EBV detected in
CSF.

- Participants with R/R disease must have had at least one prior line of systemic
therapy and one of the following: radiographic disease progression per Lugano
Classification during or after treatment or failure to achieve a CR or PR
(defined by Lugano radiographic criteria) after standard first-line therapy

- Participant may have systemic and CNS disease or CNS disease only

- For participants with EBV+ PTLD, including CD20-negative disease:

- Biopsy-proven EBV+ PTLD for whom standard first-line therapy (rituximab and/or
chemotherapy) is inappropriate, as determined by the investigator

- Participants must have systemic disease measurable per Lugano Classification
criteria, except when contraindicated or mandated by local practice, then MRI may
be used

- For participants with sarcoma, including LMS, or smooth muscle tumors:

- EBV+ sarcoma or smooth muscle tumor with rapidly progressive disease defined as
progressive disease per RECIST 1.1 criteria as documented radiographically within
a 6-month interval prior to enrollment

- Participants with newly diagnosed EBV+ sarcoma for whom the standard first-line
therapy is inappropriate, as determined by the investigator

- Biopsy-proven EBV+ sarcoma meeting one of the criteria's of pathologically
confirmed EBV+ Leiomyosarcoma or EBV+ sarcoma or smooth muscle tumor

- Measurable disease using diagnostic CT and/or MRI following RECIST 1.1 criteria
(Eisenhauer et al. 2009. Eur J Cancer 45[2]:228-247)

Exclusion Criteria:

- Currently active Burkitt, T-cell, natural killer/T-cell lymphoma/LPD, Hodgkin,
plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or
other malignancies requiring systemic therapy

- Serious known active infections, defined as ongoing uncontrolled adenovirus infection
or infections requiring systemic therapy at the time of enrollment, or known history
of human immunodeficiency virus (HIV) infection

- Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the
Center for International Blood and Marrow Transplant Research (CIBMTR) consensus
grading system or extensive chronic GvHD per National Institutes of Health (NIH)
consensus criteria at the time of the enrollment

- Need for vasopressor or ventilatory support at the time of enrollment

- Prior therapy (in order of increasing washout period) prior to enrollment as follows:

- Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational
product and/ or any chemotherapy (systemic or intrathecal), targeted small
molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody
use is permitted within the washout period if a subsequent disease response
assessment indicates disease progression

- Within 8 weeks: prior tabelecleucel (>8 weeks prior to enrollment) is permitted
if response was obtained or if usual protocol-directed therapeutic options were
not exhausted, for cellular therapies (chimeric antigen receptor therapies
directed at T-cells or T-cell subsets, donor lymphocyte infusion, other CTLs or
virus-specific T-cells); and/or therapies which could impact tabelecleucel
function (anti-thymocyte globulin, alemtuzumab)

- Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above

- Women who are breastfeeding or pregnant

- Unwilling to comply with protocol specified contraceptive/reproductive restrictions
from enrollment through 90 days after the last treatment

- Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid
equivalent, ongoing methotrexate, or extracorporeal photopheresis (for participants
with CNS disease, protocol-specified dexamethasone is permitted and concludes by the
time of enrollment)

- Any conditions that may put the study outcomes at undue risk (life expectancy < 60
days or any life-threatening illness, medical condition, or organ system dysfunction)

- For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid
organ transplant

- For participants with EBV+ PTLD: prior systemic therapy for PTLD

21-114