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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)

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ClinicalTrials.gov Identifier: NCT03394365
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
Atara Biotherapeutics

Tracking Information
First Submitted Date  ICMJE December 29, 2017
First Posted Date  ICMJE January 9, 2018
Last Update Posted Date March 25, 2020
Actual Study Start Date  ICMJE December 29, 2017
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2019)
Objective response rate (ORR) in the SOT or HCT cohort [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2018)
Objective response rate (ORR) [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2019)
  • Duration of response (DOR) in SOT and HCT cohorts separately [ Time Frame: 2 years ]
  • ORR and DOR in SOT and HCT cohorts combined [ Time Frame: 2 years ]
  • Rates of complete response (CR) and partial response (PR) [ Time Frame: 2 years ]
  • Time to response [ Time Frame: 2 years ]
  • Time to best response [ Time Frame: 2 years ]
  • Overall survival (OS) [ Time Frame: 2 years ]
  • Rates of allograft loss or rejection episodes (SOT cohort) [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2018)
  • Overall survival (OS) [ Time Frame: 5 years ]
  • Incidence of related and unrelated adverse events (AE), including AEs of interest [ Time Frame: 2 years ]
  • Patient reported outcome: EQ-5D [ Time Frame: 2 years ]
  • Patient reported outcome: Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) [ Time Frame: 2 years ]
  • Duration of response (DOR) [ Time Frame: 2 years ]
  • Rate of durable response [ Time Frame: 2 years ]
  • PTLD progression-free survival (PFS) following best response [ Time Frame: 2 years ]
  • Time to progression [ Time Frame: 2 years ]
  • Rates of allograft loss or rejection episodes [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
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).

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)
  • Solid Organ Transplant Complications
  • Lymphoproliferative Disorders
  • Allogeneic Hematopoietic Cell Transplant
  • Stem Cell Transplant Complications
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: SOT cohort -Subgroup A
    Participants who have failed rituximab will receive IV tabelecleucel.
    Intervention: Biological: tabelecleucel
  • Experimental: SOT cohort -Subgroup B
    Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.
    Intervention: Biological: tabelecleucel
  • Experimental: HCT cohort
    Participants who have failed rituximab will receive IV tabelecleucel.
    Intervention: Biological: tabelecleucel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 4, 2018)
66
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 monotherapy (SOT cohort, subgroup A or HCT cohort) or rituximab plus chemotherapy (SOT cohort, subgroup B) for treatment of PTLD.
  6. Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged > 16 years; Lansky score ≥ 20 for subjects from birth to 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 (TBILI) each < 5 × the upper limit of normal (ULN); however, ALT, AST, and TBILI each ≤ 10 × ULN 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 (eg, elevated prothrombin time due to liver dysfunction, signs/symptoms of liver dysfunction such as asterixis, or similar).
  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 (CIBMTR) 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 (CAR) 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Minoti Hiremath, MBBS, PhD 805-796-4080 clinicalstudies@atarabio.com
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03394365
Other Study ID Numbers  ICMJE ATA129-EBV-302
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Atara Biotherapeutics
Study Sponsor  ICMJE Atara Biotherapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Minoti Hiremath, MBBS, PhD Atara Biotherapeutics
PRS Account Atara Biotherapeutics
Verification Date March 2020

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