EBV-associated Malignancies, EBV-induced Lymphomas, Transplant Patients With EBV Viremia at High Risk of Developing a Recurrent EBV Lymphoma
Conditions
Keywords
stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, childhood Burkitt lymphoma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, stage II childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage I adult Burkitt lymphoma, T-cell large granular lymphocyte leukemia, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, AIDS-related peripheral/systemic lymphoma, HIV-associated Hodgkin lymphoma, stage I childhood small noncleaved cell lymphoma, stage I childhood large cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage II childhood large cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood small noncleaved cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, stage I mantle cell lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II grade 3 follicular lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, contiguous stage II small lymphocytic lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, noncontiguous stage II marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage I marginal zone lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, unspecified adult solid tumor, protocol specific, unspecified childhood solid tumor, protocol specific
Brief summary
The purpose of this phase I/II trial is to study the side effects and best dose of biological therapy to treat patients at high-risk or with Epstein-Barr virus-associated lymphoma or lymphoproliferative disease.
Interventions
BIOLOGICALEpstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Sponsors
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Atara Biotherapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma, or other EBV-associated malignancy OR * Severely immunocompromised patients who develop blood levels of EBV DNA exceeding 500 copies/ml DNA, and are therefore at high risk for developing an EBV LPD It is expected that five types of patients afflicted with EBV-associated lymphomas or lymphoproliferative diseases will be referred and will consent to participate in this trial. These are: 1. Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders following an allogeneic marrow transplant. 2. Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders following an allogeneic organ transplant. 3. Patients with AIDS developing EBV lymphomas or lymphoproliferative diseases as a consequence of the profound acquired immunodeficiency induced by HIV. 4. Patients who develop EBV lymphomas or lymphoproliferative diseases as a consequence of profound immunodeficiencies associated with a congenital immune deficit or acquired as a sequela of anti-neoplastic or immunosuppressive therapy. 5. Patients who develop other EBV-associated malignancies without pre-existing immune deficiency, including: EBV+ Hodgkin's and Non- Hodgkin's disease, EBV+ nasopharyngeal carcinoma, EBV+ hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma.
Exclusion criteria
The following patients will be excluded from this study: * Moribund patients who, by virtue of heart, kidney, liver, lung, or neurologic dysfunction not related to lymphoma, are unlikely to survive the 6-8 weeks required for in vitro generation and expansion of the EBV-specific T cells to be used for therapy and the subsequent 3 weeks required to achieve an initial assessment of the effects of infusions of EBV-specific T cells. * Pregnancy does not constitute a contraindication to infusions of EBV-specific T cells.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From Day 1 through 251.1 months after Day 1 dose | The ORR is defined as percentage of participants with best overall response of complete remission/response (CR) or partial remission/response (PR) based on investigator's assessment. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR is complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel; and PR is a 50 % or greater reduction in the size of all lymphomatous lesions as determined by computed tomography (CT) or magnetic resonance imaging (MRI) measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR is clearance of EBV without subsequent development of EBV+ LPD; and PR is at least a 10-fold decrease in EBV DNA levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From Day 1 through 251.1 months after Day 1 dose | The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method. |
| OS Rate at 12 Months | From Day 1 through 12 months after Day 1 dose | Percentage of participants with OS at 12 months are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method. |
| OS Follow-up Time | From Day 1 through 251.1 months after Day 1 dose | The OS at follow-up time are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method. |
| Time to Response (TTR) | From Day 1 through 251.1 months after Day 1 dose | The TTR was defined as the time from the date of the first dose of tabelecleucel or EBV-CTLs to the date of a PR or CR, whichever occurred first. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR was defined as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs; and a PR was defined as a 50 % or greater reduction in the size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR was defined as clearance of EBV without subsequent development of EBV+ LPD; and PR was defined as at least a 10-fold decrease in EBV DNA levels. |
| Clinical Benefit Rate (CBR) | From Day 1 through 251.1 months after Day 1 dose | The CBR was the proportion of participants who have achieved a CR, PR or SD assessed at least 28 days after first dose date of study drug. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel or EBVCTLs; and a PR as a \>= 50% reduction in size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, maintained for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR as clearance of EBV without subsequent development of EBV+ LPD; and PR as at least a 10-fold decrease in EBV DNA levels. The CBR was included specifically as clinically meaningful for solid tumor, namely LMS. |
Countries
United States
Participant flow
Pre-assignment details
A total of 58 participants were treated. However, 1 participant was analyzed in 2 different arms due to treatment. This participant was counted in only 1 arm for Participant Flow results and was counted in each arm for Outcome Measures.
Participants by arm
| Arm | Count |
|---|---|
| EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) Participants with EBV+ PTLD HCT who were R/R to rituximab received IV infusion of tabelecleucel on Days 1, 8, and 15 and were observed for 3 weeks. After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity. | 11 |
| EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) Participants with EBV+PTLD SOT who were R/R to rituximab and chemotherapy received IV infusion of tabelecleucel on Days 1, 8, and 15 and were observed for 3 weeks. After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity. | 4 |
| EBV+ LMS (Tab-cel Only) Participants with EBV+ LMS received IV infusion of tabelecleucel on Days 1, 8, and 15 and were observed for 3 weeks. After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity. | 5 |
| EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) Participants with EBV+PTLD HCT who were R/R to rituximab or rituximab naive received donor-derived EBV-CTL on Days 1, 8, and 15 and were observed for 3 weeks. After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity. | 23 |
| EBV+ Viremia (EBV-CTLs Only) Participants with EBV+ viremia received donor-derived EBV-CTLs on Days 1, 8, and 15 and were observed for 3 weeks. After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity. | 7 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Death | 4 | 1 | 1 | 0 | 0 | 13 | 0 | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) | EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) | EBV+ LMS (Tab-cel Only) | EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) | EBV+ Viremia (EBV-CTLs Only) | Total |
|---|---|---|---|---|---|---|
| Age, Customized <18 years | 7 Participants | 3 Participants | 4 Participants | 8 Participants | 3 Participants | 25 Participants |
| Age, Customized =>18 years | 4 Participants | 1 Participants | 1 Participants | 15 Participants | 4 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 3 Participants | 3 Participants | 17 Participants | 5 Participants | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) White | 6 Participants | 1 Participants | 3 Participants | 18 Participants | 5 Participants | 33 Participants |
| Sex: Female, Male Female | 7 Participants | 1 Participants | 2 Participants | 7 Participants | 2 Participants | 19 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 3 Participants | 16 Participants | 5 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 32 / 58 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 40 / 58 |
Outcome results
Primary
Objective Response Rate (ORR)
The ORR is defined as percentage of participants with best overall response of complete remission/response (CR) or partial remission/response (PR) based on investigator's assessment. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR is complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel; and PR is a 50 % or greater reduction in the size of all lymphomatous lesions as determined by computed tomography (CT) or magnetic resonance imaging (MRI) measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR is clearance of EBV without subsequent development of EBV+ LPD; and PR is at least a 10-fold decrease in EBV DNA levels.
Time frame: From Day 1 through 251.1 months after Day 1 dose
Population: Full analysis set included all participants who received at least one dose of study treatment (tabelecleucel or EBV-CTLs). Results from arms with \<= 3 participants (as shown in the participant flow) are excluded due to the low numbers of participants; these low numbers pose a risk for participant re-identification in these rare indications of this single center study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) | Objective Response Rate (ORR) | 63.6 Percentage of participants |
| EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) | Objective Response Rate (ORR) | 50.0 Percentage of participants |
| EBV+ LMS (Tab-cel Only) | Objective Response Rate (ORR) | 0 Percentage of participants |
| EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) | Objective Response Rate (ORR) | 43.5 Percentage of participants |
| EBV+ Viremia (EBV-CTLs Only) | Objective Response Rate (ORR) | 57.1 Percentage of participants |
Secondary
Clinical Benefit Rate (CBR)
The CBR was the proportion of participants who have achieved a CR, PR or SD assessed at least 28 days after first dose date of study drug. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel or EBVCTLs; and a PR as a \>= 50% reduction in size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, maintained for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR as clearance of EBV without subsequent development of EBV+ LPD; and PR as at least a 10-fold decrease in EBV DNA levels. The CBR was included specifically as clinically meaningful for solid tumor, namely LMS.
Time frame: From Day 1 through 251.1 months after Day 1 dose
Population: Full analysis set included all participants who received at least one dose of study treatment (tabelecleucel or EBV-CTLs). Participants who achieved CR, PR or SD were analyzed for this outcome measure. Results from arms with \<= 3 participants (as shown in the participant flow) are excluded due to the low numbers of participants; these low numbers pose a risk for participant re-identification in these rare indications of this single center study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) | Clinical Benefit Rate (CBR) | 63.6 Percentage of participants |
| EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) | Clinical Benefit Rate (CBR) | 75.0 Percentage of participants |
| EBV+ LMS (Tab-cel Only) | Clinical Benefit Rate (CBR) | 80.0 Percentage of participants |
| EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) | Clinical Benefit Rate (CBR) | 47.8 Percentage of participants |
| EBV+ Viremia (EBV-CTLs Only) | Clinical Benefit Rate (CBR) | 71.4 Percentage of participants |
Secondary
OS Follow-up Time
The OS at follow-up time are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through 251.1 months after Day 1 dose
Population: Full analysis set included all participants who received at least one dose of study treatment (tabelecleucel or EBV-CTLs). Results from arms with \<= 3 participants (as shown in the participant flow) are excluded due to the low numbers of participants; these low numbers pose a risk for participant re-identification in these rare indications of this single center study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) | OS Follow-up Time | 14.82 Months |
| EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) | OS Follow-up Time | 63.56 Months |
| EBV+ LMS (Tab-cel Only) | OS Follow-up Time | 77.40 Months |
| EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) | OS Follow-up Time | 18.63 Months |
| EBV+ Viremia (EBV-CTLs Only) | OS Follow-up Time | 62.98 Months |
Secondary
OS Rate at 12 Months
Percentage of participants with OS at 12 months are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through 12 months after Day 1 dose
Population: Full analysis set included all participants who received at least one dose of study treatment (tabelecleucel or EBV-CTLs). Results from arms with \<= 3 participants (as shown in the participant flow) are excluded due to the low numbers of participants; these low numbers pose a risk for participant re-identification in these rare indications of this single center study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) | OS Rate at 12 Months | 54.5 Percentage of participants |
| EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) | OS Rate at 12 Months | 75.0 Percentage of participants |
| EBV+ LMS (Tab-cel Only) | OS Rate at 12 Months | 100.0 Percentage of participants |
| EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) | OS Rate at 12 Months | 52.2 Percentage of participants |
| EBV+ Viremia (EBV-CTLs Only) | OS Rate at 12 Months | 85.7 Percentage of participants |
Secondary
Overall Survival (OS)
The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through 251.1 months after Day 1 dose
Population: Full analysis set included all participants who received at least one dose of study treatment (tabelecleucel or EBV-CTLs). Results from arms with \<= 3 participants (as shown in the participant flow) are excluded due to the low numbers of participants; these low numbers pose a risk for participant re-identification in these rare indications of this single center study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) | Overall Survival (OS) | 14.8 Months |
| EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) | Overall Survival (OS) | 84.8 Months |
| EBV+ LMS (Tab-cel Only) | Overall Survival (OS) | NA Months |
| EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) | Overall Survival (OS) | 18.6 Months |
| EBV+ Viremia (EBV-CTLs Only) | Overall Survival (OS) | NA Months |
Secondary
Time to Response (TTR)
The TTR was defined as the time from the date of the first dose of tabelecleucel or EBV-CTLs to the date of a PR or CR, whichever occurred first. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR was defined as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs; and a PR was defined as a 50 % or greater reduction in the size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR was defined as clearance of EBV without subsequent development of EBV+ LPD; and PR was defined as at least a 10-fold decrease in EBV DNA levels.
Time frame: From Day 1 through 251.1 months after Day 1 dose
Population: Full analysis set included all participants who received at least one dose of study treatment (tabelecleucel or EBV-CTLs). Participants who achieved CR or PR were analyzed for this outcome measure. Results from arms with \<= 3 participants (as shown in the participant flow) are excluded due to the low numbers of participants; these low numbers pose a risk for participant re-identification in these rare indications of this single center study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) | Time to Response (TTR) | 1.18 Months |
| EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) | Time to Response (TTR) | 6.74 Months |
| EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) | Time to Response (TTR) | 1.45 Months |
| EBV+ Viremia (EBV-CTLs Only) | Time to Response (TTR) | 1.22 Months |