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Trial record 1 of 4 for:    ALLELE | EBV
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Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03394365
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
Atara Biotherapeutics

Study Description
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Brief Summary:
The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Condition or disease Intervention/treatment Phase
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD) Solid Organ Transplant Complications Lymphoproliferative Disorders Allogeneic Hematopoietic Cell Transplant Stem Cell Transplant Complications Biological: tabelecleucel Phase 3

Expanded Access : An investigational treatment associated with this study is temporarily not available outside the clinical trial.   More info ...

Detailed Description:

This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of rituximab and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab (HCT cohort).

Enrollment will be preceded by confirmation of availability of partially human leukocyte antigen (HLA) matched and restricted tabelecleucel for the participant.

Study procedures and product administration will be the same for each cohort. Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, participants will receive intravenous tabelecleucel at a dose of 2×10^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35. Treatment will continue until maximal response, unacceptable toxicity, initiation of non protocol therapy, or failure of tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT cohort). The study includes a total of 5 years of follow-up for disease and survival status.

This protocol has been amended to include the HCT cohort from clinical study ATA129-EBV-301 (NCT03392142).

NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status "active, not recruiting" due to COVID-19 restrictions.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy
Actual Study Start Date : December 29, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Viral Infections

Arms and Interventions
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Arm Intervention/treatment
Experimental: SOT cohort -Subgroup A
Participants who have failed rituximab will receive IV tabelecleucel.
 Biological: tabelecleucel
Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
Other Names:
  • tab-cel®
  • ATA129
  • EBV-CTL
Experimental: SOT cohort -Subgroup B
Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.
 Biological: tabelecleucel
Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
Other Names:
  • tab-cel®
  • ATA129
  • EBV-CTL
Experimental: HCT cohort
Participants who have failed rituximab will receive IV tabelecleucel.
 Biological: tabelecleucel
Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
Other Names:
  • tab-cel®
  • ATA129
  • EBV-CTL


Outcome Measures
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Primary Outcome Measures :
  1. Objective response rate (ORR) in the SOT or HCT cohort [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Duration of response (DOR) in SOT and HCT cohorts separately [ Time Frame: 2 years ]
  2. ORR and DOR in SOT and HCT cohorts combined [ Time Frame: 2 years ]
  3. Rates of complete response (CR) and partial response (PR) [ Time Frame: 2 years ]
  4. Time to response [ Time Frame: 2 years ]
  5. Time to best response [ Time Frame: 2 years ]
  6. Overall survival (OS) [ Time Frame: 2 years ]
  7. Rates of allograft loss or rejection episodes (SOT cohort) [ Time Frame: 2 years ]

Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort)
  2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD
  3. Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
  4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used.For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
  5. Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (SOT subgroup A or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT subgroup B) for treatment of PTLD.
  6. Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects < 16 years
  7. For HCT cohort only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the subject underwent transplant must be in morphologic remission

  8. Adequate organ function

    1. Absolute neutrophil count ≥ 1000/μL, (SOT cohort) or ≥ 500/μL (HCT cohort), with or without cytokine support
    2. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For HCT cohort, platelet count < 50,000/μL but ≥ 20,000/μL, with or without transfusion support, is permissible if the subject has not had grade ≥ 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events [CTCAE], version 5.0)
    3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each < 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction
  9. Subject or subject's representative is willing and able to provide written informed consent

Exclusion Criteria:

  1. Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
  2. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
  3. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
  4. Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment
  5. Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment
  6. For HCT cohort: active adenovirus viremia
  7. Need for vasopressor or ventilatory support
  8. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
  9. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (SOT or HCT cohorts), or unselected donor lymphocyte infusion within 8 weeks of enrollment (HCT cohort only)
  10. Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
  11. Inability to comply with study-related procedures
Contacts and Locations
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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): NCT03394365


Contacts
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Contact: Aditi Mehta, DO 650-278-8930 ext 1 clinicalstudies@atarabio.com

Locations
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Sponsors and Collaborators
Atara Biotherapeutics
Investigators
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Study Director: Aditi Mehta, DO Atara Biotherapeutics
More Information
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Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT03394365    
Obsolete Identifiers: NCT03392142
Other Study ID Numbers: ATA129-EBV-302
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: June 24, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Atara Biotherapeutics:
Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD)
Epstein-Barr Virus (EBV)
Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL)
Cytotoxic T lymphocyte (CTL)
Cancer After Transplant
Kidney transplant
Renal transplant
Liver transplant
Heart transplant
Lung transplant
 Intestinal transplant
Pancreas transplant
Post-transplant Lymphoma
Solid Organ Transplant (SOT)
Bone Marrow Transplant Complications
Hematopoietic Cell Transplant (HCT)
Hematopoietic Stem Cell Transplantation (HSCT)
Allogeneic Hematopoietic Cell Transplant
Allogeneic, Off-The-Shelf T-cell Immunotherapy
Additional relevant MeSH terms:
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Epstein-Barr Virus Infections
Lymphoproliferative Disorders
Virus Diseases
Infections
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections