Emergency Use of Donor Lymphocytes in Treating Patients Who Have Undergone Donor Stem Cell Transplant and Have Cytomegalovirus Infections

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00769613
First received: October 8, 2008
Last updated: December 17, 2013
Last verified: August 2010
  Purpose

RATIONALE: White blood cells that have been treated in the laboratory may kill cells that are infected with cytomegalovirus.

PURPOSE: This phase I trial is studying how well cytotoxic T cells work in treating patients who have undergone donor stem cell transplant and have cytomegalovirus infections.


Condition Intervention Phase
Cancer
Biological: cytomegalovirus IE-1-specific cytotoxic T lymphocytes
Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes
Biological: therapeutic allogeneic lymphocytes
Genetic: polymerase chain reaction
Other: flow cytometry
Other: immunological diagnostic method
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Emergency Access to C.V. pp65 / IE-1 Specific Cytotoxic T Lymphocytes for Recipients of Allogeneic Stem Cell Transplants With Persistant or Therapy Refractory Infections

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Cytomegalic Inclusion Disease Ovarian Epithelial Cancer Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Acute Lymphoblastic Leukemia Testicular Cancer Multiple Myeloma Chronic Myeloproliferative Disorders Hodgkin Lymphoma Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic/myeloproliferative Disease Neuroblastoma Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Myelofibrosis Juvenile Myelomonocytic Leukemia Burkitt Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Kidney Cancer Renal Cancer Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Chronic Neutrophilic Leukemia Wilms' Tumor Hypereosinophilic Syndrome Acute Myeloid Leukemia, Childhood Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Gestational Trophoblastic Tumor Ovarian Germ Cell Tumor Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to development of cytomegalovirus (CMV)-specific immune reconstitution [ Designated as safety issue: No ]
  • CMV DNA levels [ Designated as safety issue: No ]
  • Time during post-infusion follow-up at which the dominant CMV pp65- and IE-1 epitopes for the donor is recognized by the cytotoxic T-cell lymphocytes (CTL) [ Designated as safety issue: No ]
  • Feasibility of CMV pp65- and IE-1 CTL culture after CMV vaccination of seronegative donors [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: August 2008
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To provide access to cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T lymphocytes (CTL) in patients with persistent CMV infections after allogeneic stem cell transplantation.

Secondary

  • To characterize CMV pp65- and IE-1-specific immune responses in terms of cytotoxicity and cytokine production pre-infusion and then periodically thereafter.
  • To characterize the levels of CMV DNA in recipients of CMV pp65- and IE-1-specific CTL and observe whether the CTL infusion has any impact on level of virus.
  • To determine the feasibility of CMV CTL culture from CMV-seronegative donors who have received a CMV vaccine.

OUTLINE: This is a multicenter study.

Patients receive allogeneic cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T-cell lymphocytes infusion over 5 minutes on day 1. Patients may receive up to 2 more doses at least 2 weeks after previous dose.

Blood samples are collected and analyzed by quantitative CMV PCR, chromium-release assays for CMV pp65- and IE-1-specific cytotoxicity, and immunophenotype for CD3, CD4, CD8, CD56, CD19, and CD45RA/RO. Intracellular cytofluorometry is used to assess IL-2, IL-4, IL-10, and IFN-γ production by CD4 and CD8 CMV-specific effector cells.

After completion of study therapy, patients are followed periodically for up to 1 year.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Recipient of an allogeneic stem cell transplantation
  • Cytomegalovirus (CMV)-seropositive and meeting 1 of the following criteria:

    • Patient has a history of CMV antigenemia for ≥ 2 weeks
    • CMV DNA levels ≥ 600 copies/mcg of DNA despite antiviral therapy targeting CMV (e.g., ganciclovir or foscarnet)
  • No ongoing graft-vs-host disease
  • Has donor available for peripheral blood mononuclear cell collection (for cytotoxic T lymphocytes production), meeting either of the following criteria:

    • CMV-seropositive donor (≥ 2 years of age)
    • CMV-seronegative related donor (≥ 18 years of age) who consents to receive the CMV vaccine

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-3 OR Lansky PS 50-100% (for patients < 16 years of age)
  • Bilirubin < 2.0 mg/dL
  • AST and ALT < 2.5 times normal
  • Creatinine clearance ≥ 30 mL/min
  • Pulse oximetry ≥ 94% on no more than 40% oxygen by face mask
  • Not moribund
  • No patients expected to survive ≤ 1 month after the T-cell infusion due to cardiac, pulmonary, renal, hepatic, or neurologic dysfunction

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Must be on ≤ 1 mg/kg/day of prednisone or its equivalent at the time of study CTL infusion
  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: NCT00769613

Locations
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: Kenneth G. Lucas, MD Milton S. Hershey Medical Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00769613     History of Changes
Other Study ID Numbers: CDR0000615167, PSCI-PSHCI-08-051
Study First Received: October 8, 2008
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma

Additional relevant MeSH terms:
Cytomegalovirus Infections
Emergencies
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Disease Attributes
Pathologic Processes
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 20, 2014