Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00002663
First received: November 1, 1999
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Unspecified Childhood Solid Tumor, Protocol Specific
Biological: allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Potential of adoptive immunotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • In vivo biodistribution, expansion, and duration of engraftment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence, kinetics, and durability of pathological and/or clinical responses [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 84
Study Start Date: March 1995
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes

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.

Biological: allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002663

Contacts
Contact: Richard O'Reilly, MD 212-639-5957
Contact: Susan Prockop, MD 212-639-6715

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Richard J. O'Reilly, MD    212-639-5957      
Contact: Susan Prockop, MD    212-639-6715      
Principal Investigator: Richard O'Reilly, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Richard J. O'Reilly, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00002663     History of Changes
Other Study ID Numbers: 95-024, P30CA008748, MSKCC-95024, NCI-V95-0685
Study First Received: November 1, 1999
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
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

Additional relevant MeSH terms:
Neoplasms
Lymphoma
Leukemia
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014