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Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With EBV+ PTLD After Failure of Rituximab (MATCH)

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ClinicalTrials.gov Identifier: NCT03392142
Recruitment Status : Recruiting
First Posted : January 5, 2018
Last Update Posted : October 18, 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 allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Condition or disease Intervention/treatment Phase
Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder Biological: tabelecleucel Phase 3

Expanded Access : 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 allogeneic HCT after failure of rituximab.

Tabelecleucel will be selected for the subject from the 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. Sites will provide high resolution subject and subject's graft donor HLA typing results and other information as required by the protocol.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab (MATCH 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 x 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 multiple tabelecleucel cell products.
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




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. PTLD progression-free survival (PFS) following best response [ Time Frame: 2 years ]
  4. Rate of durable response [ Time Frame: 2 years ]
  5. Time to progression [ Time Frame: 2 years ]
  6. Patient reported outcome: EQ-5D [ Time Frame: 2 years ]
  7. Patient reported outcome: Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) [ Time Frame: 2 years ]
  8. Incidence of related and unrelated adverse events (AE), including AEs of special interest [ Time Frame: 2 years ]


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:   No
Criteria

Inclusion Criteria:

  1. Prior allogeneic hematopoietic cell transplant
  2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample available for central review
  3. Availability of appropriate partially HLA-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). Baseline scans must be of acceptable quality to the central radiology laboratory prior to Cycle 1 Day 1.
  5. Failure of rituximab for first-line 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. Underlying primary disease, for which the subject underwent transplant, is in morphologic remission
  9. Adequate organ function

    1. Absolute neutrophil count ≥ 500/µL, with or without cytokine support
    2. Platelet count ≥ 50,000/µL, with or without transfusion support; 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 6 months (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 (TBILI) each < 3 x the upper limit of normal (ULN); however, ALT, AST, and TBILI each ≤ 5 x ULN is acceptable if the elevation is considered by the investigator to be due to PTLD involvement of the liver
    4. Creatinine < 3 x ULN
  10. 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. History of central nervous system (CNS) PTLD
  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 (eg, nivolumab, pembrolizumab, ipilimumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1
  5. Active adenovirus viremia
  6. Need for vasopressor or ventilatory support
  7. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to Cycle 1 Day 1
  8. Treatment with Epstein-Barr virus cytotoxic T lymphocytes, chimeric antigen receptor (CAR)-T cells directed against B cells, or unselected donor lymphocyte infusion (DLI) within 8 weeks of Cycle 1 Day 1
  9. Pregnancy
  10. 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

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): NCT03392142


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

Locations
United States, Florida
University of Miami Leonard M. Miller School of Medicine - Miami Transplant Institute (Adults only) Recruiting
Miami, Florida, United States, 33136
Contact: Amer Beitinjaneh, MD    305-243-9127    abeitinjaneh@miami.edu   
United States, Georgia
Winship Cancer Institute of Emory University (Adults only) Recruiting
Atlanta, Georgia, United States, 30322
Contact: Edmund Waller, MD    404-727-4995    ewaller@emory.edu   
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Research Center (Adults and Pediatrics) Recruiting
Chicago, Illinois, United States, 60611
Contact: Sonali Chaudhury, MD    312-227-4090    schaudhury@luriechildrens.org   
Loyola University Medical Center (Adults and Pediatrics) Recruiting
Maywood, Illinois, United States, 60153
Contact: Patrick 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 (Pediatrics only) Recruiting
Bronx, New York, United States, 10467
Contact: David Loeb, MD, PhD    718-741-2342    dloeb@montefiore.org   
Weill Cornell Medical College (Adults only) Recruiting
New York, New York, United States, 10021
Contact: Koen Van Besien, MD    646-962-7950    kov9001@med.cornell.edu   
Memorial Sloan Kettering Cancer Center (Adults and Pediatrics) Recruiting
New York, New York, United States, 10065
Contact: Susan Prockop, MD    212-639-6715    prockops@mskcc.org   
United States, North Carolina
UNC Hospitals (Adults and Pediatrics) Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Marcie Riches, MD    919-966-7746    marcie_riches@med.unc.edu   
United States, Oregon
Oregon Health and Science University (Adults and Pediatrics) Recruiting
Portland, Oregon, United States, 97239
Contact: Eneida Nemecek, MD    503-494-5058    nemeceke@ohsu.edu   
United States, Tennessee
St. Jude Children's Research Hospital (Pediatrics only) Recruiting
Memphis, Tennessee, United States, 38105
Contact: Ashok Srinivasan, MD    901-595-4720    ashok.srinivasan@stjude.org   
United States, Texas
University of Texas MD Anderson Cancer Center (Adults and Pediatrics) Recruiting
Houston, Texas, United States, 77030
Contact: Kris Mahadeo, MD    713-792-6620    kmmahadeo@mdanderson.org   
Australia, New South Wales
Westmead Hospital (Adults only) Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Abir Bhattacharyya, BSc, MBBS, MMed, FRACP, FRCPA    +61 (2) 9845 7073    abir.bhattarcharyya@health.nsw.gov.au   
Australia, South Australia
Royal Adelaide Hospital (Adults only) Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Devendra Hiwase, MD, PhD, MBBS, FRCPA, FRACP    +61 (8) 7074 4133    devendra.hiwase@sa.gov.au   
Australia, Victoria
The Royal Melbourne Hospital or The Peter MacCallum Cancer Centre (Adults only) Recruiting
Parkville, Victoria, Australia, 3050
Contact: David Ritchie, FRACP, FRCPA    +61 (3) 9342 2519    david.ritchie@mh.org.au   
Australia, Western Australia
Fiona Stanley Hospital (Adults only) Recruiting
Murdoch, Western Australia, Australia, 6150
Contact: Duncan Purtill, MBBS, FRACP, FRCPA    +61 (0) 8 6152 4139    duncan.purtill@health.wa.gov.au   
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: NCT03392142     History of Changes
Other Study ID Numbers: ATA129-EBV-301
First Posted: January 5, 2018    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 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:
Allogeneic Hematopoietic Cell Transplant
EBV-LPD
Lymphoproliferative Disorders
Epstein-Barr Virus
EBV-PTLD
alloHCT
Post-transplant lymphoproliferative disease
EBV-associated PTLD
Post-transplant lymphoma
HCT
HSCT
Cytotoxic T lymphocytes
EBV-CTL
Hematopoietic Cell Transplant
Stem cell transplant
Bone marrow transplant complications
Cancer after transplant
Allogeneic, off-the-shelf T-cell immunotherapy

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