Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma

EBV Clinical Trial

— CITADEL  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01948180
• Other study ID #: CM-2013-01
• Status: Terminated
• Phase: Phase 2
• Start date: September 2014
• Est. completion date: September 7, 2018

Study information

• Verified date: March 2019
• Source: Cell Medica Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: September 7, 2018
• Est. primary completion date: April 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• EBV
• Lymphoma
• Lymphoma, Extranodal NK-T-Cell

Intervention

Biological:
• baltaleucel-T
Autologous EBV-specific T-cells

Locations

Country	Name	City	State
France	Universitaire Ouest	Paris
France	Centre Hospitalier de Lyon	Pierre Bénite
Korea, Republic of	Asan Cancer Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
United Kingdom	University College London Hospital	London	UK
United Kingdom	The Christie Clinic	Manchester	UK
United States	Dana-Farber Cancer Center	Boston	Massachusetts
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Baylor College of Medicine	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Cell Medica Ltd

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunological assessment of EBV-specific T-cell activity and phenotyping		1 year
Other	Monitor levels of plasma and whole blood EBV DNA (viral load)		1 year
Primary	Overall response rate	Defined as best observed response (complete response or partial response) per Lugano 2014 Disease Response Criteria.	1 year
Secondary	Complete Response Rate		1 year
Secondary	Response Duration		2 years
Secondary	Time to Response		1 year
Secondary	Progression Free Survival		2 years
Secondary	Disease Free Survival		2 years
Secondary	Overall Survival		2 years
Secondary	Adverse Events		1 year