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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 ongoing, but not recruiting participants.
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: March 10, 2017
Last verified: March 2017
December 21, 2011
March 10, 2017
December 2011
January 2018   (Final data collection date for primary outcome measure)
Efficacy as defined by response rate [ Time Frame: 1 year ]
efficacy [ Time Frame: 3 weeks ]
The responses of the clinically and/or radiologically evident EBV LPD or malignancies will be identified three weeks post-infusion cycle as complete remission, partial remission, stable disease, or no response with disease progression.
Complete list of historical versions of study NCT01498484 on ClinicalTrials.gov Archive Site
  • 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 ]
remaining EBV-LPD free [ Time Frame: 6 months ]
Complete remission: Complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of affected tissues when indicated, lasting for at least three weeks following completion of a course of cell infusions.
Not Provided
Not Provided
 
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
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
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.
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
  • 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
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.
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.
Intervention: Biological: EBV-specific T cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
112
January 2018
January 2018   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
Child, Adult, Senior
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01498484
11-130
Not Provided
Not Provided
Not Provided
Not Provided
Atara Biotherapeutics
Atara Biotherapeutics
Memorial Sloan Kettering Cancer Center
Principal Investigator: Susan Prockop, MD Memorial Sloan Kettering Cancer Center
Atara Biotherapeutics
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP