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

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ClinicalTrials.gov Identifier: NCT01948180
Recruitment Status : Recruiting
First Posted : September 23, 2013
Last Update Posted : August 8, 2017
Sponsor:
Information provided by (Responsible Party):
Cell Medica Ltd

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 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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

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



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 ]


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01948180


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

Responsible Party: Cell Medica Ltd
ClinicalTrials.gov Identifier: NCT01948180     History of Changes
Other Study ID Numbers: CM-2013-01
First Posted: September 23, 2013    Key Record Dates
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