Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma (CITADEL)

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)

To investigate the efficacy of autologous EBV-specific T-cells for the treatment of patients with aggressive EBV positive extranodal NK/T-cell lymphoma

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Extranodal NK-T-Cell; EBV
• Intervention / Treatment: Biological: baltaleucel-T

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Universitaire Ouest
  • Pierre Bénite, France, 69310
    • centre hospitalier de Lyon
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Cancer Center
• United Kingdom
  • UK
    • London, UK, United Kingdom, NW1 2PG
      • University College London Hospital
    • Manchester, UK, United Kingdom, M20 4BX
      • The Christie Clinic
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: baltaleucel-T; Treatment consists of 2 infusions of 2x10E7 cells/m2 given on Days 1 and 15 intravenously via a peripheral or central line over a 1 to 10 minute period. Subjects who tolerate the study treatment well and who do not require treatment with an alternative chemotherapeutic agent will be eligible for up to 3 additional infusions of 2x10E7 cells/m2 administered at week 8, month 3 and month 6.

Biological: baltaleucel-T; Autologous EBV-specific T-cells; Other Names: CMD-003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Defined as best observed response (complete response or partial response) per Lugano 2014 Disease Response Criteria.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	2 years
Overall Survival	2 years
Adverse Events	1 year
Complete Response Rate	1 year
Response Duration	2 years
Time to Response	1 year
Disease Free Survival	2 years

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Cell Medica Ltd
• Investigators: Study Director: Kurt Gunter, MD, Cell Medica

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2014
• Primary Completion (ACTUAL): April 16, 2018
• Study Completion (ACTUAL): September 7, 2018

Study Registration Dates

• First Submitted: September 13, 2013
• First Submitted That Met QC Criteria: September 19, 2013
• First Posted (ESTIMATE): September 23, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: T cell; Epstein-Barr Virus; Natural Killer; NKTCL; CITADEL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma; Lymphoma, Extranodal NK-T-Cell
• Other Study ID Numbers: CM-2013-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO