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ATA129 for Solid Organ Transplant Subjects With 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 : January 9, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
This is a multicenter, open-label, single-arm phase 3 trial to assess the efficacy and safety of ATA129 for the treatment of Epstein Barr Virus-associated post-transplant lymphoproliferative disease (EBV-PTLD) in the setting of solid organ transplant (SOT) after failure of rituximab or rituximab plus chemotherapy.

Condition or disease Intervention/treatment Phase
EBV-Related PTLD Biological: ATA129 Phase 3

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

Detailed Description:

This is a multicenter, open-label, single-arm phase 3 trial to assess the efficacy and safety of ATA129 for the treatment of EBV-PTLD in the setting of SOT after failure of rituximab or rituximab plus chemotherapy.

ATA129 cell products will be selected for the subject from a bank of available ATA129 cell products based on matching ≥ 2 HLA alleles, at least one of which is a restricting HLA allele, shared between the ATA129 donor and the subject's EBV-PTLD.

Subjects will be enrolled into one of two cohorts based on therapy prior to enrollment: Cohort A, for those who have failed rituximab alone; and Cohort B, for those who have failed rituximab and have also received chemotherapy for the treatment of PTLD. Study procedures and product administration will be the same for each cohort.

ATA129 will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive IV ATA129 at a dose of 2×10^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Open Label, Phase 3 Trial of ATA129 for Solid Organ Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE Study)
Actual Study Start Date : December 29, 2017
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: ATA129
ATA129 will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive intravenous (IV) ATA129 at a dose of 2×10^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35.
Biological: ATA129
ATA129 is an allogeneic cellular immunotherapy for the treatment of EBV-associated malignancies and diseases.
Other Names:
  • tabelecleucel
  • tab cel™
  • EBV-CTLs


Outcome Measures

Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 5 years ]
  2. Incidence of related and unrelated adverse events (AE), including AEs of interest [ Time Frame: 2 years ]
  3. Patient reported outcome: EQ-5D [ Time Frame: 2 years ]
  4. Patient reported outcome: Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) [ Time Frame: 2 years ]
  5. Duration of response (DOR) [ Time Frame: 2 years ]
  6. Rate of durable response [ Time Frame: 2 years ]
  7. PTLD progression-free survival (PFS) following best response [ Time Frame: 2 years ]
  8. Time to progression [ Time Frame: 2 years ]
  9. Rates of allograft loss or rejection episodes [ Time Frame: 2 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
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
  2. A diagnosis of locally-assessed, biopsy-proven EBV-PTLD with a pathology sample available for central review
  3. Availability of appropriate HLA partially-matched and restricted ATA129 cell product
  4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease (using Lugano Classification response criteria) by positron emission tomography (PET)/computed tomography (CT). For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal magnetic resonance imaging (MRI) as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
  5. Treatment failure of rituximab monotherapy (Cohort A) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (Cohort B) for treatment of PTLD
  6. Males and females of any age
  7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 for subjects aged > 16 years; Lansky score ≥ 20 for subjects from birth to 16 years
  8. Adequate organ function

    1. Absolute neutrophil count ≥ 1000/μL, with or without cytokine support
    2. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support
    3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin < 3×ULN; however, ALT, AST, and TBILI each ≤ 5×ULN is acceptable if the elevation is considered due to PTLD involvement of the liver.
    4. Creatinine < 3×ULN
  9. Subject or subject's representative is willing and able to provide written informed consent

Exclusion Criteria:

  1. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, methotrexate, or extracorporeal photopheresis
  2. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment at enrollment
  3. Grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system at enrollment
  4. Ongoing or recent use of a checkpoint inhibitor agent (eg ipilimumab, pembrolizumab, nivolumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1
  5. Need for vasopressor or ventilatory support
  6. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to Cycle 1 Day 1
  7. Previous treatment with EBV-targeted cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of Cycle 1 Day 1
  8. Pregnancy
  9. Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
  10. Inability to comply with study procedures
Contacts and Locations

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
Contact: Atara Biotherapeutics (805) 603-4856 clinicaltrials@atarabio.com

Locations
United States, Florida
Leonard M. Miller School of Medicine - Miami Transplant Institute Recruiting
Miami, Florida, United States, 33136
Contact: Amer Beitinjaneh, MD, MPH, MSc    305-243-6626    abeitinjaneh@miami.edu   
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Lisa Gennarini, MD    718-920-2460    lfigueir@montefiore.org   
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Ran Reshef, MD    212-342-0530    rr3036@cumc.columbia.edu   
Sponsors and Collaborators
Atara Biotherapeutics
Investigators
Study Director: Willis H Navarro, MD Atara Biotherapeutics
Study Director: Akshay Sudhindra, MD Atara Biotherapeutics
More Information

Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT03394365     History of Changes
Other Study ID Numbers: ATA129-EBV-302
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Atara Biotherapeutics:
Solid organ transplant
EBV-PTLD
Cytotoxic T Lymphocytes
SOT
Lymphoproliferative disorders
Post-transplant lymphoproliferative disease
EBV-CTL
Epstein-Barr Virus
Kidney transplant
Renal transplant
Liver transplant
Heart transplant
Lung transplant
Intestinal transplant
Pancreas transplant
Organ transplant complications

Additional relevant MeSH terms:
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents