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

Primary Purpose

Cancer

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cytomegalovirus IE-1-specific cytotoxic T lymphocytes
cytomegalovirus pp65-specific cytotoxic T lymphocytes
therapeutic allogeneic lymphocytes
polymerase chain reaction
flow cytometry
immunological diagnostic method
laboratory biomarker analysis
Sponsored by
Milton S. Hershey Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cancer focused on measuring 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, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent/refractory childhood Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous 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 mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), atypical chronic myeloid leukemia, BCR-ABL1 negative, blastic phase chronic myelogenous leukemia, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, juvenile myelomonocytic leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, childhood myelodysplastic syndromes, chronic eosinophilic leukemia, primary myelofibrosis, chronic neutrophilic leukemia, de novo myelodysplastic syndromes, disseminated neuroblastoma, myelodysplastic/myeloproliferative neoplasm, unclassifiable, high risk metastatic gestational trophoblastic tumor, previously treated childhood rhabdomyosarcoma, previously treated myelodysplastic syndromes, recurrent Wilms tumor and other childhood kidney tumors, recurrent childhood rhabdomyosarcoma, recurrent neuroblastoma, recurrent ovarian epithelial cancer, recurrent ovarian germ cell tumor, recurrent malignant testicular germ cell tumor, secondary myelodysplastic syndromes, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, stage III malignant testicular germ cell tumor, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, refractory multiple myeloma, cytomegalovirus infection

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

Outcomes

Primary Outcome Measures

Safety
Toxicity

Secondary Outcome Measures

Time to development of cytomegalovirus (CMV)-specific immune reconstitution
CMV DNA levels
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)
Feasibility of CMV pp65- and IE-1 CTL culture after CMV vaccination of seronegative donors

Full Information

First Posted
October 8, 2008
Last Updated
December 17, 2013
Sponsor
Milton S. Hershey Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00769613
Brief Title
Emergency Use of Donor Lymphocytes in Treating Patients Who Have Undergone Donor Stem Cell Transplant and Have Cytomegalovirus Infections
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2010
Overall Recruitment Status
Unknown status
Study Start Date
August 2008 (undefined)
Primary Completion Date
August 2014 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Milton S. Hershey Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
Keywords
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, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent/refractory childhood Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous 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 mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), atypical chronic myeloid leukemia, BCR-ABL1 negative, blastic phase chronic myelogenous leukemia, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, juvenile myelomonocytic leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, childhood myelodysplastic syndromes, chronic eosinophilic leukemia, primary myelofibrosis, chronic neutrophilic leukemia, de novo myelodysplastic syndromes, disseminated neuroblastoma, myelodysplastic/myeloproliferative neoplasm, unclassifiable, high risk metastatic gestational trophoblastic tumor, previously treated childhood rhabdomyosarcoma, previously treated myelodysplastic syndromes, recurrent Wilms tumor and other childhood kidney tumors, recurrent childhood rhabdomyosarcoma, recurrent neuroblastoma, recurrent ovarian epithelial cancer, recurrent ovarian germ cell tumor, recurrent malignant testicular germ cell tumor, secondary myelodysplastic syndromes, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, stage III malignant testicular germ cell tumor, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, refractory multiple myeloma, cytomegalovirus infection

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
cytomegalovirus IE-1-specific cytotoxic T lymphocytes
Intervention Type
Biological
Intervention Name(s)
cytomegalovirus pp65-specific cytotoxic T lymphocytes
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Type
Genetic
Intervention Name(s)
polymerase chain reaction
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Type
Other
Intervention Name(s)
immunological diagnostic method
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Primary Outcome Measure Information:
Title
Safety
Title
Toxicity
Secondary Outcome Measure Information:
Title
Time to development of cytomegalovirus (CMV)-specific immune reconstitution
Title
CMV DNA levels
Title
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)
Title
Feasibility of CMV pp65- and IE-1 CTL culture after CMV vaccination of seronegative donors

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth G. Lucas, MD
Organizational Affiliation
Milton S. Hershey Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn State Cancer Institute at Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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