An Evaluation of the Toxicity and Therapeutic Effects of Epstein-Barr Virus-Immune (EBV)-Immune T-Lymphocytes Derived From Normal HLA-Compatible or Haplotype-Matched Donor in the Treatment of EBV-Associated Lymphoproliferative Diseases or Malignancies and Patients With Detectable Circulating Levels of EBV DNA Who Are at High Risk for EBV-Associated Lymphoproliferative Diseases
N/A
N/A
Both
Leukemia, Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
An Evaluation of the Toxicity and Therapeutic Effects of Epstein-Barr Virus-Immune (EBV)-Immune T-Lymphocytes Derived From Normal HLA-Compatible or Haplotype-Matched Donor in the Treatment of EBV-Associated Lymphoproliferative Diseases or Malignancies and Patients With Detectable Circulating Levels of EBV DNA Who Are at High Risk for EBV-Associated Lymphoproliferative Diseases
OBJECTIVES:
- Determine the toxicity and therapeutic potential of adoptive immunotherapy with Epstein
Barr virus (EBV)-specific cytotoxic T lymphocytes derived from HLA-histocompatible
related donors or haplotype-matched donor in the treatment of patients at high-risk or
with EBV-induced lymphomas and other lymphoproliferative diseases or malignancies in
immunocompromised hosts.
- Complete a single selected dose level phase II extension of this study to identify the
probability of achieving a CR of EBV lymphoma with EBV-specific T-cell therapy in
allogeneic HSCT recipients and immunodeficient patients.
- Evaluate in vivo biodistribution, expansion, and duration of engraftment of successive
doses of EBV-reactive lymphocytes within immunocompromised histocompatible hosts with
EBV-associated lymphoproliferative diseases, and correlate these findings with the
patients' T-cell populations, general immune status, and capacity to generate
allospecific antidonor response.
- Determine incidence, kinetics, and durability of pathologic and/or clinical responses
in this patient population treatment with infusions of these EBV-specific T cells.
OUTLINE: This is a dose-escalation study. Patients are stratified according to graft vs host
disease risk (high vs low).
Patients receive adoptive immunotherapy with allogeneic Epstein Barr virus (EBV)-specific
cytotoxic T lymphocytes IV on days 1, 8, and 15. Courses repeat every 3 weeks in the absence
of disease progression or unacceptable toxicity.
The dose of allogeneic EBV-specific cytotoxic T lymphocytes is escalated in cohorts of 3-6
patients until the maximum-tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
After completion of study treatment, patients are followed periodically for 1 year.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Pathologically documented Epstein-Barr virus (EBV) antigen-positive at risk or with
lymphoproliferative disease, lymphoma, or other EBV-associated malignancy
- Immunocompromised as a consequence of:
- Genetic or acquired immunodeficiency (including AIDS)
- Allogeneic bone marrow or organ transplant
- Normal lymphocyte donor related to patient or, for organ allografts, to organ*:
- Immunocompetent
- HLA compatible
- EBV seropositive
- HIV negative
- Organ donors at least HLA haplotype-identical with the lymphoma NOTE: *However,
if the HSCT donor is EBV seronegative or not available (e.g., a cord blood
transplant), EBV-specific T-cells generated from a normal seropositive related
or unrelated donor matched for at least 2 HLA alleles may be used.
PATIENT CHARACTERISTICS:
Age:
- Not specified
Performance status:
- No moribund patients
Life expectancy:
- At least 9 weeks
Hematopoietic:
- Not specified
Hepatic:
- Not specified
Renal:
- Not specified
Other:
- Pregnant women eligible
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Not specified
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity
Outcome Time Frame:
2 years
Safety Issue:
Yes
Principal Investigator
Richard J. O'Reilly, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
95-024
NCT ID:
NCT00002663
Start Date:
March 1995
Completion Date:
March 2014
Related Keywords:
- Leukemia
- Lymphoma
- Unspecified Adult Solid Tumor, Protocol Specific
- Unspecified Childhood Solid Tumor, Protocol Specific
- stage I adult Hodgkin lymphoma
- stage II adult Hodgkin lymphoma
- stage III adult Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- recurrent adult Hodgkin lymphoma
- stage I cutaneous T-cell non-Hodgkin lymphoma
- stage II cutaneous T-cell non-Hodgkin lymphoma
- stage III cutaneous T-cell non-Hodgkin lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- childhood Burkitt lymphoma
- stage I childhood lymphoblastic lymphoma
- stage II childhood lymphoblastic lymphoma
- stage III childhood lymphoblastic lymphoma
- stage IV childhood lymphoblastic lymphoma
- recurrent childhood lymphoblastic lymphoma
- childhood diffuse large cell lymphoma
- childhood immunoblastic large cell lymphoma
- stage II childhood Hodgkin lymphoma
- stage I childhood Hodgkin lymphoma
- stage III childhood Hodgkin lymphoma
- stage IV childhood Hodgkin lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- stage I grade 1 follicular lymphoma
- stage I grade 2 follicular lymphoma
- stage I grade 3 follicular lymphoma
- stage I adult diffuse small cleaved cell lymphoma
- stage I adult diffuse mixed cell lymphoma
- stage I adult diffuse large cell lymphoma
- stage I adult immunoblastic large cell lymphoma
- stage I adult lymphoblastic lymphoma
- stage I adult Burkitt lymphoma
- T-cell large granular lymphocyte leukemia
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III adult Burkitt lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult Burkitt lymphoma
- stage I adult T-cell leukemia/lymphoma
- stage II adult T-cell leukemia/lymphoma
- stage III adult T-cell leukemia/lymphoma
- stage IV adult T-cell leukemia/lymphoma
- recurrent adult T-cell leukemia/lymphoma
- AIDS-related peripheral/systemic lymphoma
- HIV-associated Hodgkin lymphoma
- stage I childhood small noncleaved cell lymphoma
- stage I childhood large cell lymphoma
- stage II childhood small noncleaved cell lymphoma
- stage II childhood large cell lymphoma
- stage III childhood small noncleaved cell lymphoma
- stage III childhood large cell lymphoma
- stage IV childhood small noncleaved cell lymphoma
- stage IV childhood large cell lymphoma
- recurrent childhood small noncleaved cell lymphoma
- recurrent childhood large cell lymphoma
- stage I mantle cell lymphoma
- contiguous stage II grade 1 follicular lymphoma
- contiguous stage II grade 2 follicular lymphoma
- contiguous stage II grade 3 follicular lymphoma
- contiguous stage II adult diffuse small cleaved cell lymphoma
- contiguous stage II mantle cell lymphoma
- contiguous stage II adult diffuse mixed cell lymphoma
- contiguous stage II adult immunoblastic large cell lymphoma
- contiguous stage II adult diffuse large cell lymphoma
- contiguous stage II adult Burkitt lymphoma
- contiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- recurrent mantle cell lymphoma
- stage I mycosis fungoides/Sezary syndrome
- stage II mycosis fungoides/Sezary syndrome
- stage III mycosis fungoides/Sezary syndrome
- stage IV mycosis fungoides/Sezary syndrome
- recurrent mycosis fungoides/Sezary syndrome
- contiguous stage II small lymphocytic lymphoma
- contiguous stage II marginal zone lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- noncontiguous stage II marginal zone lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage I marginal zone lymphoma
- stage I small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- unspecified adult solid tumor, protocol specific
- unspecified childhood solid tumor, protocol specific
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
