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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

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ClinicalTrials.gov Identifier: NCT01498484
Recruitment Status : Active, not recruiting
First Posted : December 23, 2011
Last Update Posted : February 28, 2018
Sponsor:
Collaborator:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Atara Biotherapeutics

Brief Summary:
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 or disease Intervention/treatment 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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : December 2011
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




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

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


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
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)

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): NCT01498484


Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Atara Biotherapeutics
Memorial Sloan Kettering Cancer Center
Investigators
Principal Investigator: Susan Prockop, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT01498484     History of Changes
Other Study ID Numbers: 11-130
First Posted: December 23, 2011    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: February 2018

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