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Safety and Effectiveness of EBV-specific Cytotoxic T Cells for the Treatment for EBV Lymphomas or Other EBV-associated Malignancies

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03988582
Recruitment Status : Withdrawn (Lack of accrual)
First Posted : June 17, 2019
Last Update Posted : June 11, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE June 13, 2019
First Posted Date  ICMJE June 17, 2019
Last Update Posted Date June 11, 2020
Actual Study Start Date  ICMJE June 11, 2019
Actual Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2019)
best overall response rate [ Time Frame: 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Effectiveness of EBV-specific Cytotoxic T Cells for the Treatment for EBV Lymphomas or Other EBV-associated Malignancies
Official Title  ICMJE A Phase II Trial of EBV-Specific Cytotoxic T Cells for the Treatment of EBV Lymphomas or Other EBV-associated Malignancies
Brief Summary The purpose of this study is to test whether treatment with EBV-specific cytotoxic T cells (EBV-CTLs) is effective, and to test any good and bad effects of treatment with EBV-CTLs. EBV-CTLs are a special immune cells that may attack abnormal cells. EBV-CTLs are made by taking cells from a healthy person, growing them in a laboratory for several weeks to educate them to recognize and destroy EBV infected cells, and then storing them in a freezer until they are required for treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • EBV Lymphomas
  • EBV-associated Malignancies
Intervention  ICMJE Biological: EBV-specific T-cells
During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period.
Study Arms  ICMJE
  • Experimental: HCT (hematopoietic cell transplant) recipients
    EBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response).
    Intervention: Biological: EBV-specific T-cells
  • Experimental: SOT (solid organ transplant) recipients
    EBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response).
    Intervention: Biological: EBV-specific T-cells
  • Experimental: Other immune competent or immune compromised patients
    EBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response).
    Intervention: Biological: EBV-specific T-cells
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 Withdrawn
Actual Enrollment  ICMJE
 (submitted: June 9, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: June 13, 2019)
79
Actual Study Completion Date  ICMJE June 8, 2020
Actual Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • A patient will be considered eligible to receive EBV-CTL treatment if the following inclusion criteria are met. Patients should receive established effective therapy if it exists and they can tolerate it prior to enrolling on protocol to receive experimental therapy. Patients will be considered eligible regardless of initial response to rituximab (alloHCT recipients) rituximab and/or multi-agent chemotherapy (SOT and other immune compromised recipients) and appropriate first line chemotherapy (non immune compromised recipients).
  • Three cohorts of patients will be eligible for enrollment:

    °Cohort 1

  • Patients after allogeneic HCT who have:

    1. EBV+ malignancies
    2. EBV viremia (as evidenced by two serial plasma EBV DNA assays) without EBV+ malignancy

Included in cohort 1 will be patients with underlying immunodeficiency syndromes with:

3. EBV+ malignancies 4. EBV viremia without current but with a history of prior EBV+ malignancy

  • Cohort 2

    • Patients after allogeneic SOT who have:

      1. EBV+ malignancies
      2. EBV viremia (as evidenced by two serial plasma EBV DNA assays) without current but with a history of prior EBV+ malignancy.
    • Patients in Cohort 1 (D) and 2 (B) treated for EBV viremia without evidence of EBV+ malignancy will need to have a history of a prior EBV malignancy with:
    • Continued viremia at the completion of planned therapy
    • Recurrence of viremia within 2 months from completion of planned therapy
    • High grade viremia (>20,000 copies) after treatment for EBV malignancy
    • Evidence of EBV positivity for patients in cohort 1 and 2 is determined as follows:
    • A biopsy showing EBV+ malignancy or
    • A combination of EBV viremia AND radiographic appearance consistent with an EBV+ malignancy
  • Cohort 3

A. EBV-associated lymphomas and lymphoproliferative disorders not associated with immunodeficiency (biopsy required) (e.g. EBV+ Hodgkin lymphoma, etc).

- Based on prior studies, patients with NK/T lymphoma will only be eligible for protocol if EBV-CTL therapy is being administered from their HCT donor either prior to or after HCT.

B. Other EBV-associated malignancies (biopsy required) including nasopharyngeal carcinoma, EBV+ gastric cancer, EBV+ leiomyosarcoma.

  • Patients in cohort 3 will be assessed for whether alternative standard therapy is available prior to being consented to the trial.
  • Patients in cohort 3 will need a biopsy showing EBV+ disease.
  • Patients in cohort 3 will not be treated for viremia alone.

All Patients:

  1. Availability of EBV-CTLs generated specifically for the patient and demonstrated to be restricted by a shared HLA-allele.
  2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 for patients aged > 16 years; Lansky score ≥ 20 for patients ≤ 16 years
  3. For patients with PTLD in the alloHCT setting, the underlying disease for which alloHCT transplant was performed is either an EBV+ malignancy or in morphologic remission
  4. Adequate organ function per the following (unless deemed to be caused by the underlying EBV-driven process which EBV-CTLs are intended to treat, or its prior therapy):

    A. Absolute neutrophil count ≥ 500/μL, with or without cytokine support B. Platelet count ≥ 20,000/μL, with or without transfusion support C. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3× the upper limit of normal (ULN) and total bilirubin < 2.5×ULN; D. Creatinine < 3×ULN

  5. Patient or patient's representative is willing and able to provide written informed consent

Exclusion Criteria:

  1. Any concomitant investigational therapy that would impair the ability to assess efficacy or toxicity of the EBV-CTL treatment. Simultaneous initiation of rituximab therapy in a patient who has received no prior rituximab.
  2. Uncontrolled graft versus host disease or organ rejection or ongoing need for methotrexate, extracorporeal photopheresis, or corticosteroids at a dose greater than 0.5mg/kg/day prednisone or equivalent.
  3. Need for vasopressor or ventilatory support, unless deemed to be caused by the EBV-driven process which EBV-CTLs are intended to treat
  4. Pregnancy
  5. Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
  6. Inability to comply with study procedures
  7. Patients who have received allogenic cells from a donor other than their HCT or SOT donor within 30 days.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT03988582
Other Study ID Numbers  ICMJE 18-315
Has Data Monitoring Committee Not Provided
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: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Susan Prockop, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date June 2020

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