EBV, Lymphoma, Extranodal NK-T-Cell
Conditions
Keywords
NKTCL, T cell, CITADEL, Epstein-Barr Virus, Natural Killer
Brief summary
To investigate the efficacy of autologous EBV-specific T-cells for the treatment of patients with aggressive EBV positive extranodal NK/T-cell lymphoma
Interventions
BIOLOGICALbaltaleucel-T
Autologous EBV-specific T-cells
Sponsors
Cell Medica Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
FOR SCREENING PHASE: Inclusion Criteria: 1. Diagnosis of extranodal NK/T lymphoma, per WHO classification, 4th ed., which must include EBV tumor positivity, measured either by EBV encoded RNA (EBER) or LMP1 immunostaining. 2. a) Active Disease (1) Clinically suspected or documented relapse/progression, in first or second relapse following at least one cycle of an asparaginase-based chemotherapy regimen OR (2) Initial disease or first or second relapse and unable to tolerate one full cycle of asparaginase-based chemotherapy regimen OR b) High-risk disease (stage III/IV, KPI groups 3-4 or IPI intermediate-high) prior to second CR regardless of previous chemotherapy. 3\. Male or female ≥ 18 years of age. 4. Weigh ≥ 35 kg. 5. ECOG performance score 0-2, inclusively. 6. Negative β-hCG test in women of childbearing potential. 7. Able to understand and comply with the requirements of the study and to provide written informed consent.
Exclusion criteria
1. CNS lymphoma. 2. NK cell leukemia. 3. Hemophagocytic lymphohistiocytosis. 4. Positive for HIV, hepatitis B, hepatitis C, syphilis or human T Cell leukemia virus (HTLV). 5. Use of systemic corticosteroids \>0.5 mg/kg/day within 10 days prior to obtaining 200 mL whole blood starting material. 6. Patient is pregnant or lactating. 7. Active second malignancy. 8. Any prior allogeneic hematopoietic stem cell or solid organ transplant. 9. Asparaginase refractory disease, defined by any one of the following: 1. Progression at any time during initial asparaginase based chemotherapy and up to 3 months after end of initial asparaginase based chemotherapy, OR 2. Failure to achieve at least PR with initial asparaginase based chemotherapy. 10. Absolute lymphocyte count (ALC) \<400/µL. 11. Any previous autologous EBV specific T cell treatment. 12. Systemic fungal, bacterial, viral or other infection that is not controlled. 13. Third or greater relapse. FOR TREATMENT PHASE: Inclusion Criteria: 1. Documented relapse or progression following at least one prior cycle of an asparaginase-containing chemotherapy regimen. 2. Active disease based on any one of the following present at the baseline study visit or within two weeks prior to the baseline study visit: 1. Imaging (may use local imaging) 2. Clinical sign(s) including skin lesions consistent with lymphoma, organ dysfunction or organomegaly not attributable to other causes; or other clinical sign(s) 3. Detectable blood or plasma ENV DNA (may use local laboratory) 3. Completed most recent course of chemotherapy at least 2 weeks prior to first study drug dose. 4. Recovery from acute hematological, hepatic and renal chemotherapy-related toxicities as defined by ≤ Grade 1 according to NCI CTCAE v4.0. 5. Life expectancy ≥ 8 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | 1 year | Defined as best observed response (complete response or partial response) per Lugano 2014 Disease Response Criteria. |
Secondary
| Measure | Time frame |
|---|---|
| Complete Response Rate | 1 year |
| Response Duration | 2 years |
| Time to Response | 1 year |
| Progression Free Survival | 2 years |
| Overall Survival | 2 years |
| Adverse Events | 1 year |
| Disease Free Survival | 2 years |
Other
| Measure | Time frame |
|---|---|
| Immunological assessment of EBV-specific T-cell activity and phenotyping | 1 year |
| Monitor levels of plasma and whole blood EBV DNA (viral load) | 1 year |
Countries
France, South Korea, United Kingdom, United States
Outcome results
None listed