Know Cancer

or
forgot password

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


Phase 1/Phase 2
N/A
N/A
Open (Enrolling)
Both
Leukemia, Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific

Thank you

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 CenterNew York, New York  10021