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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Recruitment Status : Withdrawn (Lack of accrual)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

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.

Condition or disease Intervention/treatment Phase
EBV Lymphomas EBV-associated Malignancies Biological: EBV-specific T-cells Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of EBV-Specific Cytotoxic T Cells for the Treatment of EBV Lymphomas or Other EBV-associated Malignancies
Actual Study Start Date : June 11, 2019
Actual Primary Completion Date : June 8, 2020
Actual Study Completion Date : June 8, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
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).
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.

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).
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.

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).
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.




Primary Outcome Measures :
  1. best overall response rate [ Time Frame: 6 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03988582


Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Susan Prockop, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03988582    
Other Study ID Numbers: 18-315
First Posted: June 17, 2019    Key Record Dates
Last Update Posted: June 11, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
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)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
cytotoxic T cells
HLA-haplotype
18-315
Additional relevant MeSH terms:
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Lymphoma
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases