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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-01932 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Infection prophylaxis and management may help prevent cytomegalovirus (CMV) infection caused by a stem cell transplant.
PURPOSE:This clinical trial studies infection prophylaxis and management in treating cytomegalovirus infection in patients with hematologic malignancies previously treated with donor stem cell transplant.
PRIMARY OBJECTIVES:
I. To evaluate the efficacy and safety of a individualized strategy for cytomegalovirus (CMV) preemptive management, one that monitors CMV viral load and clinical markers of immunosuppression to optimize use of ganciclovir in recipients of allogeneic hematopoietic cell transplantation (HCT) who experience CMV reactivation.
SECONDARY OBJECTIVES:
I. To investigate how donor killer-cell immunoglobulin-like receptors (KIR) genes of interest (activating KIR2DS2 and 2DS4, inhibitory KIR2DL1, 2DL2/2DL3, 3DL1, 3DL2), together with their recipient ligands where known, influence CMV reactivation-free survival after allogeneic HCT, independently of clinical risk factors such as onset of acute graft-versus-host disease.
II. To investigate whether markers of natural killer (NK) cell function correlate with a) KIR/ligand compound genotype and baseline or concurrent clinical factors and b) with history of CMV reactivation and anti-CMV therapy at the time of NK cell collection.
III. To investigate associations between NK cell recovery and antigen-specific T cell immune reconstruction.
OUTLINE: Patients receive standard antiviral infection prophylaxis and management comprising ganciclovir, valganciclovir, or foscarnet sodium for 2 weeks or until the plasma CMV deoxyribonucleic acid (DNA) quantitative polymerase chain reaction (Q-PCR) is negative. Patients may receive additional courses based on subsequent CMV reactivations.
After completion of study treatment, patients are followed up for up to 1 year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Patients receive standard antiviral infection prophylaxis and management comprising ganciclovir, valganciclovir, or foscarnet sodium for 2 weeks or until the plasma CMV DNA Q-PCR is negative. Patients may receive additional courses based on subsequent CMV reactivations. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| infection prophylaxis and management | Procedure | Undergo infection prophylaxis and management |
|
| Measure | Description | Time Frame |
|---|---|---|
| Initiation of anti-CMV therapy | Subjects will not be considered treated with anti-CMV agents unless at least 4 consecutive days of therapy are completed. | Day 80 post stem cell transplant |
| Diagnosis of CMV pneumonia | Confirmed by detection of CMV in bronchoalveolar lavage or lung biopsy. Reported overall and separately for those whose preemptive management was and was not modified (postponed or foregone or limited to a false start) and compared to corresponding incidence in a similar cohort at our institution. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| CMV reactivation-free survival, monitored using a real time PCR assay for CMV DNA in plasma | Modeled using proportional hazards regression. Primary risk factors will be donor KIR of interest (activating KIR2DS2 and 2DS4, inhibitory KIR2DL1, 2DL2/2DL3, 3DL1, 3DL2), together with their recipient ligands where known. Potential confounding factors to be controlled in the model will include established clinical risk factors, including pretransplant CMV serostatus of donor and recipient, unrelated donor, marrow versus peripheral blood stem cells, and onset of acute graft-versus-host disease, handled as a time-dependent variable. The proportionality of hazards over time will be verified. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ryotaro Nakamura | City of Hope Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Medical Center | Duarte | California | 91010 | United States |
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| laboratory biomarker analysis | Other | Correlative studies |
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| flow cytometry | Other | Correlative studies |
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| DNA analysis | Genetic | Correlative studies |
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| RNA analysis | Genetic | Correlative studies |
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| management of therapy complications | Procedure | undergo infection prophylaxis and management |
|
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| ganciclovir | Drug | Given IV |
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| valganciclovir | Drug | Given orally |
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| foscarnet sodium | Drug | Given orally |
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| antiviral therapy | Procedure | undergo infection prophylaxis and management |
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| polymerase chain reaction | Genetic | Correlative studies |
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| protein expression analysis | Genetic | Correlative studies |
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| Up to day 100 post-transplant |
| Percent cytotoxicity and ex vivo percent CD56+/CD107B+ cells | Studied longitudinally in generalized linear models. Each of the 2 markers of NK function will be modeled separately. | Day 120 post stem cell transplant |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D015465 | Leukemia, Myeloid, Accelerated Phase |
| D015456 | Leukemia, Biphenotypic, Acute |
| D000013 | Congenital Abnormalities |
| D054391 | Lymphoma, Extranodal NK-T-Cell |
| D017728 | Lymphoma, Large-Cell, Anaplastic |
| D007119 | Immunoblastic Lymphadenopathy |
| D000741 | Anemia, Aplastic |
| D054438 | Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative |
| D001752 | Blast Crisis |
| C580364 | Pdgfra-Associated Chronic Eosinophilic Leukemia |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D015467 | Leukemia, Neutrophilic, Chronic |
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D003586 | Cytomegalovirus Infections |
| D013920 | Thrombocythemia, Essential |
| D064090 | Intraocular Lymphoma |
| D007946 | Leukemia, Mast-Cell |
| D009196 | Myeloproliferative Disorders |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D011087 | Polycythemia Vera |
| D055728 | Primary Myelofibrosis |
| D000075363 | Immunoglobulin Light-chain Amyloidosis |
| D015463 | Leukemia, Prolymphocytic |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| D002051 | Burkitt Lymphoma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D008228 | Lymphoma, Non-Hodgkin |
| D006689 | Hodgkin Disease |
| D016400 | Lymphoma, Large-Cell, Immunoblastic |
| D054218 | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma |
| D016410 | Lymphoma, T-Cell, Cutaneous |
| D008224 | Lymphoma, Follicular |
| D020522 | Lymphoma, Mantle-Cell |
| D009182 | Mycosis Fungoides |
| D012751 | Sezary Syndrome |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D007943 | Leukemia, Hairy Cell |
| D009101 | Multiple Myeloma |
| D054066 | Leukemia, Large Granular Lymphocytic |
| D008258 | Waldenstrom Macroglobulinemia |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D016399 | Lymphoma, T-Cell |
| D008223 | Lymphoma |
| D000072281 | Lymphadenopathy |
| D000740 | Anemia |
| D000080983 | Bone Marrow Failure Disorders |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D001778 | Blood Coagulation Disorders |
| D013922 | Thrombocytosis |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
| D005134 | Eye Neoplasms |
| D034721 | Mastocytosis, Systemic |
| D008415 | Mastocytosis |
| D000090362 | Mast Cell Activation Disorders |
| D016393 | Lymphoma, B-Cell |
| D019046 | Bone Marrow Neoplasms |
| D054219 | Neoplasms, Plasma Cell |
| D000686 | Amyloidosis |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010265 | Paraproteinemias |
| D020031 | Epstein-Barr Virus Infections |
| D014412 | Tumor Virus Infections |
| D015448 | Leukemia, B-Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001796 | Blood Protein Disorders |
| D015458 | Leukemia, T-Cell |
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| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D005434 | Flow Cytometry |
| D015774 | Ganciclovir |
| D000077562 | Valganciclovir |
| D017245 | Foscarnet |
| D000998 | Antiviral Agents |
| D016133 | Polymerase Chain Reaction |
| ID | Term |
|---|---|
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D000212 | Acyclovir |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D010746 | Phosphonoacetic Acid |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D000890 | Anti-Infective Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D021141 | Nucleic Acid Amplification Techniques |
| D005821 | Genetic Techniques |
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