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Therapeutic Effects of Epstein-Barr Virus Immune T-Lymphocytes Derived From a Normal HLA-Compatible Or Partially-Matched Third-Party Donor in the Treatment of EBV Lymphoproliferative Disorders and EBV-Associated Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by Atara Biotherapeutics
Sponsor:
Collaborator:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Atara Biotherapeutics
ClinicalTrials.gov Identifier:
NCT01498484
First received: December 21, 2011
Last updated: December 22, 2016
Last verified: December 2016
  Purpose
This is a Phase II trial to evaluate the efficacy and safety of human leukocyte antigen (HLA) partially-matched third-party allogeneic Epstein-Barr virus cytotoxic T lymphocytes (EBV-CTLs) for the treatment of EBV-induced lymphomas and EBV-associated malignancies.

Condition Intervention Phase
EBV-induced Lymphomas
EBV-associated Malignancies
Transplant Patients With EBV Viremia at High Risk for Developing a Recurrent EBV Lymphoma
Biological: EBV-specific T cells
Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Therapeutic Effects Of Epstein-Barr Virus Immune T-Lymphocytes Derived From a Normal HLA-Compatible Or Partially-Matched Third-Party Donor in the Treatment of EBV Lymphoproliferative Disorders and EBV-Associated Malignancies

Resource links provided by NLM:


Further study details as provided by Atara Biotherapeutics:

Primary Outcome Measures:
  • Efficacy as defined by response rate [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • In vivo expansion and duration of EBV-CTLs measured via CTLp assay over time (cells/mL/time) [ Time Frame: 1 year ]
  • Durability of clinical responses (time) [ Time Frame: 1 year ]

Estimated Enrollment: 112
Study Start Date: December 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EBV-specific T cells
Patients will each receive a course of three weekly infusions of EBV-specific T cells (EBV-CTLs). Each weekly dose will provide 2 x 10^6 T cells/kg recipient weight (+/- 3 days). After the third dose, patients will be observed for approximately 3 weeks.
Biological: EBV-specific T cells
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma or other EBV-associated malignancy.

OR

  • Evaluable disease as demonstrated by clinical and/or radiologic studies with current or prior elevated blood levels of EBV DNA exceeding 500 copies/ml by quantitative real time PCR.

OR

  • Persistent or recurrent elevations in levels of EBV DNA exceeding 500 copies/ml in patients previously treated for EBV-LPD with chemotherapy and/or rituximab who do not yet have clinically or radiologically evaluable disease but are at high risk of disease recurrence.
  • EBV-specific T cells are available for adoptive immune cell therapy from a consenting third party donor. The third party EBV-CTLs to be administered will be selected on the basis of two criteria: 1) that they are matched for at least 2 HLA antigens and 2) that they are restricted by an allele shared with the EBV+ malignancy (if known), or with the donor in HSCT recipients, or patient in organ transplant or immunodeficient patients
  • KPS or Lansky score ≥ 20.
  • A life expectancy of at least 6 weeks.
  • Adequate bone marrow, heart, lung, liver and kidney function at the time of treatment with EBV-specificT cells is initiated, including:

    1. Absolute neutrophil count (ANC) ≥ 1,000/µL, with or without GCSF support
    2. Platelets ≥ 20,000/µL
    3. Creatinine ≤ 2.0mg/dl
    4. ALT, AST < 3.0x and total bilirubin < 2.5x the institutional ULN
    5. Stable blood pressure and circulation not requiring pressor support
    6. Adequate cardiac function as demonstrated by EKG and/or echocardiographic evidence (may be performed within 30 days prior to treatment)
  • However, abnormalities of specific organs will not be considered grounds for exclusion if they are the result of the EBV+ malignancy or its treatment (e.g. a renal allograft recipient with an EBV LPD may be on dialysis because the allograft was rejected when the immune suppression was stopped as a first approach to treatment of the EBV LPD). At the discretion of the investigator, patients with elevated but stable creatinine will not be precluded from treatment on study.
  • There is no age restriction to eligibility for this protocol.

It is expected that five types of patients afflicted with EBV-associated lymphomas, lymphoproliferative diseases or malignancies will be referred and will consent to participate in this trial. These are:

  1. Patients developing EBV lymphomas or lymphoproliferative disorders following an allogeneic hematopoietic progenitor stem cell transplant (HSCT) (ie, marrow, PBSC, or umbilical cord blood).
  2. Patients developing EBV lymphomas or lymphoproliferative disorders following an allogeneic organ transplant.
  3. Patients with AIDS developing EBV lymphomas or lymphoproliferative diseases as a consequence of the profound acquired immunodeficiency induced by HIV.
  4. Patients who develop EBV lymphomas or lymphoproliferative diseases or other EBV-associated malignancy as a consequence of profound immunodeficiencies associated with a congenital immune deficit or acquired as a sequela of anti-neoplastic or immunosuppressive therapy.
  5. Patients who develop other EBV-associated malignancies without pre-existing immune deficiency, including: EBV+ Hodgkin's and Non-Hodgkin's disease, EBV+ nasopharyngeal carcinoma, EBV+ hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma.

Exclusion Criteria:

The following patients will be excluded from this study:

  • Patients with active (grade 2-4) acute graft vs. host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) requiring high doses of glucocorticosteroid (>0.5 mg/kg/day prednisone or its equivalent) as treatment
  • Patients who are pregnant
  • Patients with severe comorbidities, not related to their EBV-associated malignancy, that would be expected to preclude their survival for the 6 weeks required to assess response of T cell therapy
  • Patients eligible for MSK protocol #16-803 (EBV-CTL-201)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498484

Contacts
Contact: Susan Prockop, MD 212-639-6715
Contact: Craig Sauter, MD 212-639-3460

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Susan Prockop, MD    212-639-6715      
Contact: Craig Sauter, MD    212-639-3460      
Principal Investigator: Susan Prockop, MD         
Sponsors and Collaborators
Atara Biotherapeutics
Memorial Sloan Kettering Cancer Center
Investigators
Principal Investigator: Susan Prockop, MD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT01498484     History of Changes
Other Study ID Numbers: 11-130 
Study First Received: December 21, 2011
Last Updated: December 22, 2016

Keywords provided by Atara Biotherapeutics:
EBV-specific T-cell lines
11-130

Additional relevant MeSH terms:
Lymphoma
Neoplasms
Lymphoproliferative Disorders
Viremia
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on February 24, 2017