Clinical trial NCT01948180: Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma
Official title: A Phase 2 Single Arm Study to Investigate the Efficacy of Autologous EBV-specific T-cells for the Treatment of Patients With Aggressive EBV Positive Extranodal NK/T-cell Lymphoma (ENKTCL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma, Extranodal NK-T-Cell
EBV
Keywords: NKTCL
T cell
CITADEL
Epstein-Barr Virus
Natural Killer
Lead sponsor: Cell Medica Ltd
Sponsor class: INDUSTRY
First posted: 2013-09-23
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Exclusion Criteria:

1. Use of any investigational agents within prior 4 weeks.
2. Radiotherapy within prior 3 weeks.
3. Major surgery within prior 2 weeks.
4. Systemic corticosteroids within 24 hours prior to study drug administration.
5. Evidence of hepatic dysfunction based on serum total bilirubin \>3 times upper limit of normal (ULN), or ALT \>5 times ULN or AST \>5 times ULN.

Primary outcomes:
measure: Overall response rate
timeFrame: 1 year
Secondary outcomes:
measure: Complete Response Rate
timeFrame: 1 year
measure: Response Duration
timeFrame: 2 years
measure: Time to Response
timeFrame: 1 year
measure: Progression Free Survival
timeFrame: 2 years
measure: Disease Free Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
measure: Adverse Events
timeFrame: 1 year
Other outcomes:
measure: Immunological assessment of EBV-specific T-cell activity and phenotyping
timeFrame: 1 year
measure: Monitor levels of plasma and whole blood EBV DNA (viral load)
timeFrame: 1 year
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Paris
country: France
facility: Universitaire Ouest
city: Pierre Bénite
country: France
facility: Centre Hospitalier de Lyon
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Cancer Center
city: London
country: United Kingdom
facility: University College London Hospital
state: UK
city: Manchester
country: United Kingdom
facility: The Christie Clinic
state: UK
Study officials:
affiliation: Baylor College of Medicine
name: Helen Heslop, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cell Medica
name: Kurt Gunter, MD
role: STUDY_DIRECTOR
References: