Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies
Conditions
Leukemia - Lymphoma - Unspecified Adult Solid Tumor, Protocol Specific - Unspecified Childhood Solid Tumor, Protocol Specific
Conditions: official terms
Lymphoma - Lymphoproliferative Disorders
Conditions: Keywords
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
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes
Type: Biological
Overall Status
Recruiting
Summary
RATIONALE: Some types of lymphoma or lymphoproliferative disease are associated with Epstein-Barr virus. White blood cells from donors who are immune to Epstein-Barr virus may be an effective treatment for those cancers.

PURPOSE: This phase I/II trial is studying the side effects and best dose of biological therapy in treating patients at high-risk or with Epstein-Barr virus-associated lymphoma or lymphoproliferative disease.
Detailed Description
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: N/A
Gender: Both
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.

- Patients who develop other EBV-associated malignancies without pre-existing immune deficiency, including: EBV+ Hodgkin's and Non-Hodgkin's disease, EBV+ nasopharyngeal carcinoma, EBV+hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma. Normal, EBV specific T-cells from third party seropositive donors who are HLA compatible in at least 2 HLA alleles shared by the patient will be used. Selection of T cells known to be restricted by an HLA allele shared by the patient will be given priority.

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
Location
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Status: Recruiting
Contact: Susan J. Prockop, MD - 212-639-6715
Start Date
March 1995
Completion Date
March 2016
Sponsors
Atara Biotherapeutics
Source
Atara Biotherapeutics
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page