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

Study Description

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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

Condition or disease	Intervention/treatment	Phase
Lymphoma, Extranodal NK-T-Cell; EBV	Biological: CMD-003	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	35 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	September 2014
Estimated Primary Completion Date :	September 2018
Estimated Study Completion Date :	September 2019

Arms and Interventions

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Arm

Intervention/treatment

Experimental: CMD-003; 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: CMD-003; Autologous EBV-specific T-cells

Outcome Measures

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Primary Outcome Measures :

1. Overall response rate [ Time Frame: 1 year ]
   Defined as best observed response (complete response or partial response) per Lugano 2014 Disease Response Criteria.

Secondary Outcome Measures :

1. Complete Response Rate [ Time Frame: 1 year ]
2. Response Duration [ Time Frame: 2 years ]
3. Time to Response [ Time Frame: 1 year ]
4. Progression Free Survival [ Time Frame: 2 years ]
5. Disease Free Survival [ Time Frame: 2 years ]
6. Overall Survival [ Time Frame: 2 years ]
7. Adverse Events [ Time Frame: 1 year ]

Other Outcome Measures:

1. Immunological assessment of EBV-specific T-cell activity and phenotyping [ Time Frame: 1 year ]
2. Monitor levels of plasma and whole blood EBV DNA (viral load) [ Time Frame: 1 year ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Contacts

Contact: Shannon Inman	832-581-4474	shannon.inman@cellmedica.co.uk

Locations

United States, California
City of Hope	Recruiting
Duarte, California, United States, 91010
Contact: Rosemarie Abary 626-218-8087 rabary@coh.org
Principal Investigator: Elizabeth Budde, MD
United States, District of Columbia
Children's National Medical Center	Recruiting
Washington, D.C., District of Columbia, United States, 20010
Contact: Nana Ama K Afari-Dwamena 202-476-6768 nafaridwam@childrensnational.org
Principal Investigator: Catherine Bollard, MD
United States, Massachusetts
Dana-Farber Cancer Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Kristin McHugh 617-582-7292 KMMCHUGH@PARTNERS.ORG
Principal Investigator: Eric Jacobsen, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Kristen Arends 507-284-5736 arends.kristen@mayo.edu
Principal Investigator: Yi Lin, MD
United States, New Jersey
John Theurer Cancer Center at Hackensack UMC	Withdrawn
Hackensack, New Jersey, United States, 07601
United States, New York
New York-Presbyterian/Weill Cornell	Recruiting
New York, New York, United States, 10065
Contact: Marissa Contento 212-746-1858 mac2363@med.cornell.edu
Principal Investigator: Jia Ruan, MD
United States, Ohio
The Ohio State University Comprehensive Cancer Center	Recruiting
Columbus, Ohio, United States, 43210
Contact: Raoof Giali 614-688-7313 Raoof.Giali@osumc.edu
Principal Investigator: Jonathan Brammer, MD
United States, Texas
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Vicky Torrano 832-824-7821 vxtorran@txch.org
Principal Investigator: Helen Heslop, MD
MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Linda Claret 713-792-1044 LCClaret@mdanderson.org
Principal Investigator: Yasushiro Oki, MD
France
Centre Hospitalier Universitaire de Limoges	Recruiting
Limoges Cedex, France, 87042
Contact: Fabienne Auroy +33 (0)5 55 05 86 33 fabienne.auroy@chu-limoges.fr
Principal Investigator: Arnaud Jaccard, Prof
Universitaire Ouest	Recruiting
Paris, France, 75015
Contact: Thamila Berdous-Saheb +33 (0)1 44 49 56 83 thamila.berdous-saheb@nck.aphp.fr
Principal Investigator: Felipe Suarez, Prof
Centre Hospitalier de Lyon	Recruiting
Pierre Bénite, France, 69310
Contact: Cécile Francoise +33 (0)4 78 86 42 23 ext-cecile.francoise@chu-lyon.fr
Principal Investigator: Gilles Salles, Prof.
Germany
Charite	Withdrawn
Berlin, Germany, 13353
Askelpios Klinik St Georg	Withdrawn
Hamburg, Germany, 20099
Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Withdrawn
Mainz, Germany, 55131
Korea, Republic of
Korean Cancer Center	Recruiting
Seoul, Korea, Korea, Republic of, 139-709
Contact: Gyeong Ja Go +82-2-970-2530 bi-mil@hanmail.net
Principal Investigator: Hye Jin Kang, Prof
Severance Hospital, Yonsei University Medical Center	Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Jong Eun Lee +02-2228-4242 515riz@yuhs.ac
Principal Investigator: Jin Seok Kim
Samsung Medical Center	Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Woo Rim Lee + 02-2148-9173 wr87.lee@samsung.com
Principal Investigator: Won-Seog Kim
Asan Cancer Center	Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Hyunji Jun + 82-2-3010-3229 hyunjii@amc.seoul.kr
Principal Investigator: CheolWon Suh
United Kingdom
University College London Hospital	Recruiting
London, UK, United Kingdom, NW1 2PG
Contact: Thomas Taylor 020 3447 7834 Thomas.Taylor2@uclh.nhs.uk
Principal Investigator: Kirit Ardeshna
The Christie Clinic	Recruiting
Manchester, UK, United Kingdom, M20 4BX
Contact: Joanna Dash 0161 9187964 Joanna.Dash@christie.nhs.uk
Principal Investigator: John Radford

Sponsors and Collaborators

Cell Medica Ltd

Investigators

Principal Investigator:	Helen Heslop, MD	Baylor College of Medicine
Study Director:	Kurt Gunter, MD	Cell Medica

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Cell Medica Ltd
ClinicalTrials.gov Identifier:	NCT01948180 History of Changes
Other Study ID Numbers:	CM-2013-01
First Posted:	September 23, 2013
Last Update Posted:	August 8, 2017
Last Verified:	August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Cell Medica Ltd:

NKTCL; T cell; CITADEL; Epstein-Barr Virus; Natural Killer

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Extranodal NK-T-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders	Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin