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

This study is currently recruiting participants.
Verified March 2013 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00002663
First received: November 1, 1999
Last updated: March 4, 2013
Last verified: March 2013
History of Changes

November 1, 1999
March 4, 2013
March 1995
March 2014   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00002663 on ClinicalTrials.gov Archive Site
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Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies
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

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.

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.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Unspecified Childhood Solid Tumor, Protocol Specific
Biological: allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes
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.

Intervention: Biological: allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
84
March 2014
March 2014   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
Contact: Richard O'Reilly, MD 212-639-5957
Contact: Trudy Small, MD 212-639-5965
United States
 
NCT00002663
95-024, P30CA008748, MSKCC-95024, NCI-V95-0685
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Study Chair: Richard J. O'Reilly, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP