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Tabelecleucel for Solid Organ Transplant Subjects With EBV+ PTLD After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)

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ClinicalTrials.gov Identifier: NCT03394365
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
Atara Biotherapeutics

Brief Summary:
This is a multicenter, open-label, single-arm phase 3 study to assess the efficacy and safety of tabelecleucel 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
Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder Biological: tabelecleucel 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 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of rituximab or rituximab plus chemotherapy.

Tabelecleucel cell products will be selected for the subject from a bank of available tabelecleucel cell products based on matching ≥ 2 HLA alleles, at least one of which is a restricting HLA allele, shared between the tabelecleucel 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.

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


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 Study of Tabelecleucel 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


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



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

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


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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 tabelecleucel cell product
  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). 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. Note: Subjects with CD20 negative disease are eligible to enroll without prior anti-CD20 therapy after failure of first-line treatment (reduction of immunosuppression is not considered first-line therapy) and discussion with the sponsor's medical monitor.
  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 (TBILI) each < 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. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor (CAR) 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-related procedures

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, Connecticut
Yale University (Adults and Pediatrics) Recruiting
New Haven, Connecticut, United States, 06520
Contact: Pamela Valentino, MD    203-785-4649    pamela.valentino@yale.edu   
United States, Florida
University of Florida (Adults and Pediatrics) Recruiting
Gainesville, Florida, United States, 32610
Contact: John Fort, MD    352-273-9120    john.fort@ufl.edu   
Leonard M. Miller School of Medicine - Miami Transplant Institute (Adults only) Recruiting
Miami, Florida, United States, 33136
Contact: Amer Beitinjaneh, MD, MPH, MSc    305-243-6626    abeitinjaneh@miami.edu   
United States, Georgia
Winship Cancer Institute of Emory University (Adults only) Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jonathon Cohen, MD    404-778-3942    jonathon.cohen@emory.edu   
United States, Illinois
Loyola University Medical Center (Adults and Pediatrics) Recruiting
Maywood, Illinois, United States, 60153
Contact: Patrrick Stiff, MD    708-327-3148    pstiff@lumc.edu   
United States, Missouri
Washington University School of Medicine (Adults only) Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Armin Ghobadi, MD    314-747-8439    arminghobadi@wustl.edu   
United States, New York
Montefiore Medical Center (Adults only) Recruiting
Bronx, New York, United States, 10467
Contact: Murali Janakiram, MD    718-920-4826    mjanakir@montefiore.org   
Montefiore Medical Center (Pediatrics only) Recruiting
Bronx, New York, United States, 10467
Contact: David Loeb, MD, PhD    718-741-2342    dloeb@montefiore.org   
Columbia University Medical Center (Adults and Pediatrics) Recruiting
New York, New York, United States, 10032
Contact: Ran Reshef, MD    212-342-0530    rr3036@cumc.columbia.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia (Pediatrics only) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Nancy Bunin, MD    215-590-2255    buninn@email.chop.edu   
University of Pennsylvania (Adults only) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Donald Tsai    215-614-1846    donald.tsai@uphs.upenn.edu   
United States, Wisconsin
Froedtert Hospital & the Medical College of Wisconsin (Adults only) Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Marcelo Pasquini, MD    414-805-0700    mpasquini@mcw.edu   
Sponsors and Collaborators
Atara Biotherapeutics
Investigators
Study Director: Willis H Navarro, MD Atara Biotherapeutics
Study Director: Akshay Sudhindra, MD Atara Biotherapeutics

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: May 15, 2018
Last Verified: May 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:
Post-transplant lymphoma
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
Allogeneic, off-the-shelf T-cell immunotherapy
EBV-LPD
Cancer after transplant

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