Donor Stem Cell Transplant With No or Low-Intensity Chemotherapy Using Sirolimus and Treated Immune Cells to Treat Blood and Lymph Cancers
Study Details
Study Description
Brief Summary
Background:
Patients with cancers of the blood and immune system often benefit from transplants of stem cells from a genetically well-matched sibling. However, severe problems may follow these transplants because of the high-dose chemotherapy and radiation that accompany the procedure. Also, donated immune cells sometimes attack healthy tissues in a reaction called graft-versus-host disease (GVHD), damaging organs such as the liver, intestines and skin. To reduce toxicity of high-dose preparative chemotherapy, this study performs allogeneic transplant after low doses of chemotherapy. In an attempt to improve anti-tumor effects without increasing GVHD, this study uses donor immune cells (T helper 2 (Th2) cells) grown in the laboratory; some patients will receive standard donor immune cells (not grown in laboratory). All patients will receive immune modulating drugs sirolimus and cyclosporine to prevent GVHD.
Objective:
To determine the safety, treatment effects and rate of GVHD in patients receiving transplants that use low-intensity chemotherapy, sirolimus plus cyclosporine, and transplant booster with either Th2 cells or standard immune cells.
Eligibility:
Patients 16 to 75 years of age with acute or chronic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or myelodysplastic syndrome.
Patients must have a suitable genetically matched sibling donor and adequate kidney, heart and lung function.
Design: The protocol has three treatment groups: cohort 1, Th2 booster at two weeks post-transplant; cohort 2, standard T cell booster at two weeks post-transplant; cohort 3, multiple infusion of Th2 cells.
Condition: Hematologic Neoplasms, Myeloproliferative Disorders
Intervention: Biological; therapeutic allogeneic lymphocytes
Drug: Sirolimus
Study Type: Interventional
Study Design: Primary Purpose: Treatment
Phase: Phase II
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
Background
In protocol 99-C-0143, we evaluated a new approach to allogeneic hematopoietic stem cell transplant (HSCT) that involved intensive host T cell ablation and graft augmentation with in vitro generated donor T helper 2 (Th2) cells. Rapid full donor engraftment occurred with this regimen; however, grade II to IV acute graft versus host disease (GVHD) was not significantly reduced in Th2 cell recipients. In an attempt to improve clinical results using Th2 cell graft engineering, this second-generation Th2 cell clinical trial was developed that incorporates the following interventions: (1) In an attempt to reduce transplant-related toxicity, this protocol now uses a very low-intensity host preparative chemotherapy; (2) In an attempt to reduce GVHD, this study will utilize Th2 cells expanded in the presence of the immune modulation agent, rapamycin (sirolimus), as murine Th2 cells grown in rapamycin reduce GVHD more effectively than control Th2 cells; (3) To further reduce GVHD, subjects will receive a short-course of sirolimus therapy in addition to standard cyclosporine GVHD prophylaxis; and (4) Using this novel low-intensity transplant platform, compare in a preliminary manner the post-transplant outcome of patients receiving pre-emptive donor lymphocyte infusion (DLI) using either Th2 cells or unmanipulated donor T cells.
Objectives
In the setting of human leukocyte antigen (HLA)-matched sibling allogeneic HSCT using GVHD prophylaxis of cyclosporine and short-course sirolimus, compare in a preliminary manner the safety, feasibility, alloengraftment, clinical anti-tumor effects, and GVHD rate of low-intensity Preparative Chemotherapy with pre-emptive DLI using either Th2 cells or unmanipulated T cells at day 14 post-HSCT.
Eligibility
Subjects that are 16 to 75 years of age that have a suitable 6/6 HLA-matched sibling donor are potentially eligible. Subjects with a diagnosis of acute or chronic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or myelodysplastic syndrome are potentially eligible. Adequate kidney, cardiac, and pulmonary function are required.
Design
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Patients age 18 or older with lymphoma (all types) or chronic lymphocytic leukemia will be randomized just prior to the transplant regimen to receive DLI with either donor Th2 cells (cohort 1) or unmanipulated T cells (cohort 2); n=10 patients will be accrued to each arm provided that stopping rules pertaining to excessive GVHD or graft rejection are not met. For these randomized patients, the preparative regimen will consist of low-intensity fludarabine (120 mg/m(2)) plus cyclophosphamide (1200 mg/m(2)) and GVHD prophylaxis will consist of short-course, high-dose sirolimus followed by maintenance cyclosporine. Cohorts 1 and 2 will be compared in a preliminary manner with respect to their post-transplant outcome, in particular: (a) conversion of mixed chimerism to predominant donor chimerism; (b) rate and severity of classical acute and late acute GVHD at the day 100 and day 180 post-transplant time points; and (c) time to induction of leukemia/lymphoma remission (if entering transplant with disease) or time to relapse (if entering transplant in remission).
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Patients with non-lymphoma diagnoses, patients with lymphoma that are under the age of 18 and lymphoma patients that are projected to be unable to complete the protocol-defined therapy through day 180 post-transplant will not be randomized but will be treated on cohort 3 (n=40), which will evaluate transplantation without the Flu/Cy preparative regimen and with pre-emptive Th2 cell DLI. The primary objective of cohort 3 is to evaluate whether transplantation without a preparative regimen will reduce the rate of acute GVHD associated with Th2 cell DLI from 41% (the rate observed with the fludarabine/cyclophosphamide (Flu/Cy) preparative regimen) to a rate of 15% (6 cases out of 40).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm IVD cohort 1 (Th2 DLI) Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive) |
Drug: Fludarabine
Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Procedure: Peripheral blood stem cell (PBSC) transplantation
PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.
Procedure: Allogeneic hematopoietic stem cell transplant (HSCT)
Allogeneic Hematopoietic Stem Cell Transplant.
Drug: Filgrastim
Filgrastim: 5 mcg/kg/day subcutaneous (SC), day 6 (require absolute neutrophil count (ANC) > 1000, two values; or ANC > 5000 cells/ul on one occasion).
Other Names:
Genetic: T-Rapa cell Donor Lymphocyte Infusion (DLI)
The dose of T helper 2 (Th2) cells or unmanipulated donor T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) Th2/kg; minimum dose will be 1 x 10(7) Th2/kg).
|
Experimental: Arm IVD cohort 2 (conventional DLI) Patients receive low intensity fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3. Patients undergo DLI with unmanipulated donor T-cells on day 14 (single T- cell DLI in patients with low CD4 count between 100 and 200 inclusive) |
Drug: Fludarabine
Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Procedure: Peripheral blood stem cell (PBSC) transplantation
PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.
Genetic: T cell donor lymphocyte infusion (DLI) with unmanipulated donor T cells
The dose of the T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) T cells/kg; minimum dose will be 1 x 10(7) T cells/kg).
Procedure: Allogeneic hematopoietic stem cell transplant (HSCT)
Allogeneic Hematopoietic Stem Cell Transplant.
Drug: Filgrastim
Filgrastim: 5 mcg/kg/day subcutaneous (SC), day 6 (require absolute neutrophil count (ANC) > 1000, two values; or ANC > 5000 cells/ul on one occasion).
Other Names:
|
Experimental: Arm IVD cohort 3 (multiple Th2 DLI) Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300) |
Drug: Rituximab
Rituximab: 375 mg/m(2)/day intravenous (IV), day 1 (for cluster of differentiation 20 (CD20+) patients).
Other Names:
Drug: Fludarabine
Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Drug: Etoposide
Etoposide: 50 mg/m(2)/day continuous intravenous (CIV), days 1-4.
Other Names:
Drug: Doxorubicin
Doxorubicin:10 mg/m(2)/day continuous intravenous (CIV), days 1-4.
Other Names:
Drug: Vincristine
Vincristine: 0.4 mg/m(2)/day continuous intravenous (CIV), days 1-4.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Procedure: Peripheral blood stem cell (PBSC) transplantation
PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.
Drug: Prednisone
Prednisone: 60 mg/m(2)/day by mouth (PO), days 1-5.
Other Names:
Procedure: Allogeneic hematopoietic stem cell transplant (HSCT)
Allogeneic Hematopoietic Stem Cell Transplant.
Drug: Filgrastim
Filgrastim: 5 mcg/kg/day subcutaneous (SC), day 6 (require absolute neutrophil count (ANC) > 1000, two values; or ANC > 5000 cells/ul on one occasion).
Other Names:
Genetic: T-Rapa cell Donor Lymphocyte Infusion (DLI)
The dose of T helper 2 (Th2) cells or unmanipulated donor T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) Th2/kg; minimum dose will be 1 x 10(7) Th2/kg).
|
Experimental: Arm IVA (12-day expanded Th2 DLI) Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. |
Drug: Fludarabine
Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Procedure: Peripheral blood stem cell (PBSC) transplantation
PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.
Genetic: T cell donor lymphocyte infusion (DLI) with unmanipulated donor T cells
The dose of the T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) T cells/kg; minimum dose will be 1 x 10(7) T cells/kg).
Procedure: Allogeneic hematopoietic stem cell transplant (HSCT)
Allogeneic Hematopoietic Stem Cell Transplant.
Drug: Filgrastim
Filgrastim: 5 mcg/kg/day subcutaneous (SC), day 6 (require absolute neutrophil count (ANC) > 1000, two values; or ANC > 5000 cells/ul on one occasion).
Other Names:
|
Experimental: Arm IVB (6-day expanded Th2 DLI) Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. |
Drug: Fludarabine
Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Procedure: Peripheral blood stem cell (PBSC) transplantation
PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.
Genetic: T cell donor lymphocyte infusion (DLI) with unmanipulated donor T cells
The dose of the T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) T cells/kg; minimum dose will be 1 x 10(7) T cells/kg).
Procedure: Allogeneic hematopoietic stem cell transplant (HSCT)
Allogeneic Hematopoietic Stem Cell Transplant.
Drug: Filgrastim
Filgrastim: 5 mcg/kg/day subcutaneous (SC), day 6 (require absolute neutrophil count (ANC) > 1000, two values; or ANC > 5000 cells/ul on one occasion).
Other Names:
|
Experimental: Arm IVC (6-day expanded Th2 DLI and High-Dose Sirolimus) Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. |
Drug: Fludarabine
Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.
Other Names:
Procedure: Peripheral blood stem cell (PBSC) transplantation
PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.
Genetic: T cell donor lymphocyte infusion (DLI) with unmanipulated donor T cells
The dose of the T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) T cells/kg; minimum dose will be 1 x 10(7) T cells/kg).
Procedure: Allogeneic hematopoietic stem cell transplant (HSCT)
Allogeneic Hematopoietic Stem Cell Transplant.
Drug: Filgrastim
Filgrastim: 5 mcg/kg/day subcutaneous (SC), day 6 (require absolute neutrophil count (ANC) > 1000, two values; or ANC > 5000 cells/ul on one occasion).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Patients to Receive T Cell Infusion [first 100 days post-transplant]
T cells administered by intravenous infusion after patient received transplant.
- Percentage of Patients With ≥ Grade 2 Acute Graft Versus Host Disease (GVHD) [first 100 days post-transplant]
GVHD of the skin, liver and gut were graded on a scale of 1, 2, 3, and 4 (e.g. the grades are not added together) using the National Institutes of Health Consensus Criteria. Grade 1 is minimal GVHD, Grade 2 is moderate GVHD, Grade 3 is severe GVHD and Grade 4 is very severe GVHD. Grade 4 is a worse outcome than Grade 1.
Secondary Outcome Measures
- Detection of of Post-transplantation Cluster of Differentiation 4 (CD4)+ and CD8+ T-cell Production of T Helper 1 -2 (Th1-Th2)-Type Cytokines [First 100 days post-transplant]
Detection of cytokine secretion was done by enzyme-linked immunosorbent assay.
- Percentage of Patients With Opportunistic Infection [First 100 days post-transplant]
Participants are susceptible to opportunistic infections such as bacterial, fungal, viral, protozoan infections and more due to immune suppression from chemotherapy drugs used to treat their disease.
- Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0) [Date treatment consent signed to date off study, approximately 5 years]
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Eligibility Criteria
Criteria
- INCLUSION CRITERIA: PATIENT RECIPIENT
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Patients with hematologic malignancies, myelodysplasia, or myeloproliferative disorders, as summarized in the following table. The diagnosis must be histologically confirmed by the Laboratory of Pathology of National Cancer Institute (NCI) or Hackensack (There will be no central pathology review).
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Chronic Lymphocytic Leukemia - Disease Status: a) Relapse post-fludarabine, b) Non-Complete Response (CR) after salvage regimen.
Hodgkin's and Non-Hodgkin's Lymphoma (all types, including Mantle Cell Lymphoma)
- Disease Status: a) Primary treatment failure, b) Relapse after autologous stem cell transplant (SCT), c) Non-CR after salvage regimen
Special Cases of High-Risk Lymphoma, including but not limited to : (1) plasma dendritic cell type, 2) Hepato-splenic T cell type, 3) gamma delta pinniculitic T cell type, 4) Muco-cutaneous natural killer (NK) cell type and 5) stage III-IV nasal NK cell type- Disease Status: a) Primary treatment failure, b) Relapse after autologous, c) Non-CR after salvage regimen, d) In first CR or any later CR
Chronic Epstein Barr Virus (EBV)-associated lymphoproliferative disease a) At any point after diagnosis, including up-front therapy
Multiple Myeloma - Disease Status: a) Primary treatment failure, b) Relapse after autologous stem cell transplant (SCT), c) Non-CR after salvage regimen.
Acute Myelogenous Leukemia - Disease Status: a) CR number 1 and high-risk [excludes t(8;21), t(15;17), or inv(16)], b) CR number 2 or greater).
Acute Lymphocytic Leukemia - Disease Status: a) CR number 1 plus high-risk [t(9;22) or bcr-abl(+); t(4;11), 1(1;19), t(8;14)], b) In CR number2 or greater.
Myelodysplastic Syndrome - Disease Status: a) Refractory Anemia with Excess Blasts (RAEB), b) Refractory Anemia with Excess Blasts in Transformation (RAEB-T) (requires marrow and blood blasts less than 10% after induction chemotherapy).
Myeloproliferative disorders - Disease Status: a) Idiopathic myelofibrosis, b) Polycythemia vera, c) Essential thrombocytosis, d) Chronic myelomonocytic leukemia.
Chronic Myelogenous Leukemia (CML) - Disease Status: a) Chronic phase CML, refractory to imatinib treatment b) Accelerated phase CML. b) Accelerated phase CML
Patients with myeloproliferative disorders must be end-stage, which is primarily defined as disease severity refractory to splenectomy.
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Patient age of 16 to 75 years.
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Consenting first degree relative matched at 6/6 HLA antigens (A, B, and DR).
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Patient or legal guardian must be able to give informed consent.
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All previous intravenous therapy administered outside of the National Institutes of Health (NIH) Clinical Center must be completed at least 2 weeks prior to study entry, with recovery to less than or equal to non-hematologic grade 2 toxicity of previous therapy.
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Eastern Cooperative Oncology Group (ECOG) performance status equal to 0 or 1.
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Life expectancy of at least 3 months.
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Patients with acute leukemia must have chemotherapy sensitive disease, as defined by at least a 50% reduction in circulating absolute blast count due to the most proximal regimen.
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Left ventricular ejection fraction greater than or equal to 45%, preferably by 2-dimension (2-D) echo, or by multi-gated acquisition scan (MUGA). However, patients with left ventricular ejection fraction (LVEF) of between 35% and 44% may also be eligible provided that such patients are cleared by a Cardiology Consultation that must include a cardiac stress test.
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Corrected diffusing capacity or transfer of the lung for carbon monoxide (DLCO) greater than 50% of expected value.
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Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or equal to 50 ml/min.
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Serum total bilirubin less than 2.5 mg/dl; serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) equal 2.5 times upper limit of normal. Values above these levels may be accepted, at the discretion of the principal investigator (PI) or study chairman, if such elevations are thought to be due to liver involvement by malignancy or graft versus host disease (GVHD).
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Adequate central venous access potential.
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Potential patients referred for the study may not be eligible for the experimental protocol therapy due to reasons such as uncertainty about donor human leukocyte antigen (HLA) typing or need to control malignant disease, infection, or metabolic abnormality such as hypercalcemia on a emergent basis. Should a referred patient present to us in such a scenario, the patient will be referred back to their primary hematologist-oncologist for treatment. However, if referral back to the referring physician is not in the best interest of the patient according to the clinical judgement of the principal investigator (PI), then the patient may receive standard treatment for the malignant disease or complicating conditions (infection, metabolic problems under the current study. In other cases, a patient may have reasonable control of malignancy but does not meet the cluster of differentiation 4 (CD4) cell cut-off of 50 cells per microliter required for cohort 3 therapy; in such cases, standard care chemotherapy regimens may be administered for the specific goal of reducing the CD4 count (that is, immune depleting regimens such as the pentostatin plus cyclophosphamide combination, administered similar to the manner that we have developed on protocol 08-C- 0088). If it becomes apparent that the patient will not be able to proceed to experimental therapy, then he/she must come off study. Recipient-Subjects receiving a standard therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol. Because such standard care therapy is not experimental, it is not necessary to complete the eligibility criteria prior to receiving such standard care; however, prior to initiation of the experimental therapy, the patient must meet each of the eligibility criteria detailed above. Attempts will be made to standardize such pretransplant chemotherapy (by administration of etoposide, prednisolone, oncovin, cyclophosphamide, hydroxydaunorubicin, fludarabine, rituximab (EPOCH-FR) chemotherapy, which is detailed later in this protocol); however, other regimens using approved agents will be allowed if such regimens are thought to be in the best interest of the patient.
INCLUSION CRITERIA: DONOR
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First-degree relative with genotypic identity at 6/6 HLA loci (HLA- A, B, and DR).
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Age 11 to 90 years and able to give consent or assent. For donors < 18 years old, the legal guardian must be able to provide informed consent.
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Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis.
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Donors must be human immunodeficiency virus (HIV) negative.
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Donors with a history of hepatitis B or hepatitis C infection may be eligible. However, eligibility determination of such patients will require a hepatology consultation. The risk/benefit of the transplant and the possibility of transmitting hepatitis will be discussed with the patient and eligibility will then be determined by the principal investigator and lead associate investigator (LAI).
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Lactating donors must substitute formula feeding for her infant during period of filgrastim administration (to prevent any filgrastim effect on infant).
EXCLUSION CRITERIA: PATIENT
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Active infection that is not responding to antimicrobial therapy.
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Active central nervous system (CNS) involvement by malignancy.
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HIV infection (treatment may result in progression of HIV and other viral infections).
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Chronic active hepatitis B. Patient may be hepatitis B core antibody positive. For patients with concomitant positive hepatitis B surface antigen, patient will require a hepatology consultation. The risk/benefit profile of transplant and hepatitis B will be discussed with the patient and eligibility determined by the principal investigator and Lead Associate Investigator.
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Hepatitis C infection. Patient may have hepatitis C infection. However, each patient will require a hepatology consultation. The risk/benefit profile of transplant and hepatitis C will be discussed with the patient and eligibility determined by the principal investigator and Lead Associate Investigator.
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Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.
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History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
EXCLUSION CRITERIA: DONOR
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History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
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History of hypertension that is not controlled by medication, stroke, autoimmune disease, or severe heart disease (donors with symptomatic angina will be excluded). Donors with a history of coronary artery bypass grafting or angioplasty who are symptom free will receive a cardiology evaluation and be considered on a case-by-case basis.
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History of prior malignancy. However, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis. In addition, donors with localized cancer such as prostate cancer that are on a watch-and-wait management due to the low-risk of disease progression may also be considered for stem cell donation on a case-by-case basis. The risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient.
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Donors must not be pregnant (unknown effect of filgrastim on fetus). Donors of childbearing potential must use an effective method of contraception.
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Anemia (Hemoglobin (Hb) less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per microliter). However, potential donors with Hb levels less than 11 gm/dl that is due to iron deficiency will be eligible as long as the donor is initiated on iron replacement therapy and the case is individually approved by National Institutes of Health (NIH) or Hackensack Blood Bank.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
2 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Steven Z Pavletic, M.D., National Cancer Institute (NCI)
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. Review.
- Jamshed S, Fowler DH, Neelapu SS, Dean RM, Steinberg SM, Odom J, Bryant K, Hakim F, Bishop MR. EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011 May;46(5):676-81. doi: 10.1038/bmt.2010.173. Epub 2010 Jul 26.
- 040055
- 04-C-0055
- NCT00077480
Study Results
Participant Flow
Recruitment Details | |
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Pre-assignment Detail | Enrollment was 442 (221 donors; 221 patients). 57 recipients were treated on cohorts no longer in the protocol due to amendments. Thus, 164 of 221 recipient data is presented. No patients were eligible for therapy on arm IVD, cohort 2. |
Arm/Group Title | Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) | Healthy Donors |
---|---|---|---|---|---|---|
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). Etoposide: Etoposide: 50 mg/m(2)/day continuous intravenous (CIV), days 1-4 Doxorubicin: Doxorubicin:10 mg/m(2)/day CIV, days 1-4 Vincristine: Vincristine:0.4 mg/m(2)/day CIV, days 1-4 Cyclophosphamide: Cyclophosphamide, 750 mg/m(2)/day IV, day 5 T cell donor lymphocyte infusion (DLI) with sirolimus generated donor TH-2 cells: The cell of the Th2 cells will attempt to be held constant for each study receipient (target dose 2.5 x 107 Th2/kg; minimum dose will be 1 x 107 Th2/kg). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Donate donor immune cells for recipients. No data was collected from the donor population. |
Period Title: Overall Study | ||||||
STARTED | 1 | 34 | 40 | 44 | 45 | 221 |
COMPLETED | 1 | 27 | 40 | 44 | 42 | 221 |
NOT COMPLETED | 0 | 7 | 0 | 0 | 3 | 0 |
Baseline Characteristics
Arm/Group Title | Arm IVDcohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) | Total |
---|---|---|---|---|---|---|
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Total of all reporting groups |
Overall Participants | 1 | 34 | 40 | 44 | 45 | 164 |
Age (Count of Participants) | ||||||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
1
100%
|
33
97.1%
|
36
90%
|
41
93.2%
|
42
93.3%
|
153
93.3%
|
>=65 years |
0
0%
|
1
2.9%
|
4
10%
|
3
6.8%
|
3
6.7%
|
11
6.7%
|
Age (years) [Mean (Standard Deviation) ] | ||||||
Mean (Standard Deviation) [years] |
56
|
45.96
(12.41)
|
49.68
(12.92)
|
47.66
(12.45)
|
50.19
(13.50)
|
49.44
(13.12)
|
Sex: Female, Male (Count of Participants) | ||||||
Female |
0
0%
|
8
23.5%
|
17
42.5%
|
21
47.7%
|
13
28.9%
|
59
36%
|
Male |
1
100%
|
26
76.5%
|
23
57.5%
|
23
52.3%
|
32
71.1%
|
105
64%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||||
Hispanic or Latino |
0
0%
|
11
32.4%
|
8
20%
|
10
22.7%
|
4
8.9%
|
33
20.1%
|
Not Hispanic or Latino |
1
100%
|
23
67.6%
|
32
80%
|
34
77.3%
|
41
91.1%
|
131
79.9%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | ||||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
2
5.9%
|
0
0%
|
2
4.5%
|
1
2.2%
|
5
3%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
1
2.9%
|
4
10%
|
2
4.5%
|
4
8.9%
|
11
6.7%
|
White |
1
100%
|
20
58.8%
|
28
70%
|
30
68.2%
|
36
80%
|
115
70.1%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
11
32.4%
|
8
20%
|
10
22.7%
|
4
8.9%
|
33
20.1%
|
Region of Enrollment (Count of Participants) | ||||||
United States |
1
100%
|
34
100%
|
40
100%
|
44
100%
|
45
100%
|
164
100%
|
Outcome Measures
Title | Percentage of Patients to Receive T Cell Infusion |
---|---|
Description | T cells administered by intravenous infusion after patient received transplant. |
Time Frame | first 100 days post-transplant |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) |
---|---|---|---|---|---|
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. |
Measure Participants | 1 | 27 | 40 | 44 | 42 |
Number [percentage of patients] |
100
|
100
|
100
|
100
|
100
|
Title | Percentage of Patients With ≥ Grade 2 Acute Graft Versus Host Disease (GVHD) |
---|---|
Description | GVHD of the skin, liver and gut were graded on a scale of 1, 2, 3, and 4 (e.g. the grades are not added together) using the National Institutes of Health Consensus Criteria. Grade 1 is minimal GVHD, Grade 2 is moderate GVHD, Grade 3 is severe GVHD and Grade 4 is very severe GVHD. Grade 4 is a worse outcome than Grade 1. |
Time Frame | first 100 days post-transplant |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) |
---|---|---|---|---|---|
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. |
Measure Participants | 1 | 27 | 40 | 44 | 42 |
Number [percentage of patients] |
0
|
11.11
|
10
|
40.91
|
40.48
|
Title | Detection of of Post-transplantation Cluster of Differentiation 4 (CD4)+ and CD8+ T-cell Production of T Helper 1 -2 (Th1-Th2)-Type Cytokines |
---|---|
Description | Detection of cytokine secretion was done by enzyme-linked immunosorbent assay. |
Time Frame | First 100 days post-transplant |
Outcome Measure Data
Analysis Population Description |
---|
This outcome measure was not done. Data was not collected for this outcome measure due to premature closure of study. |
Arm/Group Title | Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) |
---|---|---|---|---|---|
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. |
Measure Participants | 0 | 0 | 0 | 0 | 0 |
Title | Percentage of Patients With Opportunistic Infection |
---|---|
Description | Participants are susceptible to opportunistic infections such as bacterial, fungal, viral, protozoan infections and more due to immune suppression from chemotherapy drugs used to treat their disease. |
Time Frame | First 100 days post-transplant |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) |
---|---|---|---|---|---|
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Arm IVB Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. |
Measure Participants | 1 | 27 | 40 | 44 | 42 |
Number [percentage of participants] |
0
0%
|
11.11
32.7%
|
7.50
18.8%
|
9.09
20.7%
|
11.90
26.4%
|
Title | Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0) |
---|---|
Description | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Time Frame | Date treatment consent signed to date off study, approximately 5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) |
---|---|---|---|---|---|
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. |
Measure Participants | 1 | 27 | 40 | 44 | 42 |
Count of Participants [Participants] |
1
100%
|
27
79.4%
|
40
100%
|
44
100%
|
42
93.3%
|
Adverse Events
Time Frame | Date treatment consent signed to date off study, approximately 5 years. | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Enrollment was 442 (221 donors; 221 patients). No data was collected from the donor population. 57 recipients were treated on cohorts no longer in the protocol due to amendments. Thus, 164 of 221 recipient data is presented. No patients were eligible for therapy on arm IVD, cohort 2. | |||||||||
Arm/Group Title | Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) | |||||
Arm/Group Description | Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive). | Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300). | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14. | |||||
All Cause Mortality |
||||||||||
Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/1 (0%) | 14/34 (41.2%) | 22/40 (55%) | 24/44 (54.5%) | 22/45 (48.9%) | |||||
Serious Adverse Events |
||||||||||
Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/1 (100%) | 22/34 (64.7%) | 37/40 (92.5%) | 35/44 (79.5%) | 31/45 (68.9%) | |||||
Blood and lymphatic system disorders | ||||||||||
Blood/Bone Marrow - Other (engraftment syndrome) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Febrile neutropenia | 0/1 (0%) | 0 | 2/34 (5.9%) | 3 | 10/40 (25%) | 11 | 25/44 (56.8%) | 25 | 5/45 (11.1%) | 5 |
Hemoglobin | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 8/40 (20%) | 14 | 10/44 (22.7%) | 16 | 3/45 (6.7%) | 4 |
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Thrombotic microangiopathy | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Cardiac disorders | ||||||||||
Cardiac Arrhythmia - Other (atrial fibrillation) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Cardiac General - Other (congestive heart failure) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Cardiac ischemia/infarction | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Conduction abnormality/atrioventricular heart block::AV Block-First degree | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Conduction abnormality/atrioventricular heart block::AV Block-Second degree Mobitz Type II | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Left ventricular diastolic dysfunction | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Left ventricular systolic dysfunction | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 2/45 (4.4%) | 2 |
Pericardial effusion (non-malignant) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Restrictive cardiomyopathy | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Supraventricular and nodal arrhythmia::Atrial fibrillation | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Supraventricular and nodal arrhythmia::Atrial flutter | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Supraventricular and nodal arrhythmia::Sinus tachycardia | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Supraventricular and nodal arrhythmia::Supraventricular tachycardia | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Endocrine disorders | ||||||||||
Pancreatic endocrine: glucose intolerance | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 5/44 (11.4%) | 5 | 0/45 (0%) | 0 |
Thyroid function, high (hyperthyroidism, thyrotoxicosis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Thyroid function, low (hypothyroidism) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Eye disorders | ||||||||||
Dry eye syndrome | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ocular/Visual - Other (GVHD) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ocular/Visual - Other (ocular GVHD, restasis started; EXTENSIVE CGVHD) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ophthalmoplegia/diplopia (double vision) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Gastrointestinal disorders | ||||||||||
Colitis | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 1/40 (2.5%) | 1 | 3/44 (6.8%) | 3 | 0/45 (0%) | 0 |
Colitis, infectious (e.g., Clostridium difficile) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 2/40 (5%) | 2 | 7/44 (15.9%) | 7 | 7/45 (15.6%) | 7 |
Diarrhea | 1/1 (100%) | 1 | 4/34 (11.8%) | 4 | 10/40 (25%) | 10 | 16/44 (36.4%) | 16 | 11/45 (24.4%) | 11 |
Dry mouth/salivary gland (xerostomia) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Dysphagia (difficulty swallowing) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 1/45 (2.2%) | 1 |
Esophagitis | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 3 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Gastritis (including bile reflux gastritis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Gastrointestinal - Other (Abdominal pain (GVHD of the gut) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Gastrointestinal - Other (abdominal pain, nausea and diarrhea c/w GVHD) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Hemorrhage, GI::Lower GI NOS | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Hemorrhage, GI::Rectum | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 2 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Hemorrhage, GI::Upper GI NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 3/45 (6.7%) | 3 |
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Mucositis/stomatitis (clinical exam)::Oral cavity | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Mucositis/stomatitis (functional/symptomatic)::Oral cavity | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Nausea | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 3/40 (7.5%) | 4 | 5/44 (11.4%) | 5 | 1/45 (2.2%) | 1 |
Obstruction, GI::Gallbladder | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Obstruction, GI::Small bowel NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Pain::Abdomen NOS | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 2/40 (5%) | 2 | 2/44 (4.5%) | 2 | 3/45 (6.7%) | 3 |
Pain::Oral cavity | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Perforation, GI::Small bowel NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Typhlitis (cecal inflammation) | 0/1 (0%) | 0 | 1/34 (2.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ulcer, GI::Stomach | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Vomiting | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
General disorders | ||||||||||
Death not associated with CTCAE term::Death NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 2/44 (4.5%) | 2 | 5/45 (11.1%) | 5 |
Death not associated with CTCAE term::Disease progression NOS | 0/1 (0%) | 0 | 7/34 (20.6%) | 8 | 9/40 (22.5%) | 9 | 12/44 (27.3%) | 12 | 11/45 (24.4%) | 11 |
Death not associated with CTCAE term::Multi-organ failure | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Death not associated with CTCAE term::Sudden death | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 14/40 (35%) | 14 | 10/44 (22.7%) | 10 | 0/45 (0%) | 0 |
Hemorrhage/Bleeding - Other (Conjunctival, low platelet ct) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Immune system disorders | ||||||||||
Allergic reaction/hypersensitivity (including drug fever) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infections and infestations | ||||||||||
Infection (documented clinically or microbiologically) | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection (documented clinically | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 8/34 (23.5%) | 9 | 5/40 (12.5%) | 6 | 13/44 (29.5%) | 13 | 1/45 (2.2%) | 1 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 7/40 (17.5%) | 7 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 3 | 3/44 (6.8%) | 3 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 2 | 1/40 (2.5%) | 1 | 12/44 (27.3%) | 12 | 2/45 (4.4%) | 2 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 4 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 3/44 (6.8%) | 3 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 1/45 (2.2%) | 1 |
Infection - Other (C.Diff: PCR +) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection - Other (HHV6 reactivation; admitted for anemia & leukocytosis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection - Other (Influenza A +) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection - Other (R. wrist septic arthritis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection - Other (pseudomonas bacteremia/sepsis.) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection - Other (worsening right great toe pain with drainage and now neutropenic) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Appendix | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Blood | 1/1 (100%) | 1 | 13/34 (38.2%) | 14 | 10/40 (25%) | 11 | 18/44 (40.9%) | 22 | 13/45 (28.9%) | 13 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Bone (osteomyelitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Brain (encephalitis, infectious) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 4/44 (9.1%) | 5 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Brain + Spinal cord (encephalomyelitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Catheter-related | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 6/40 (15%) | 6 | 4/44 (9.1%) | 4 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Colon | 1/1 (100%) | 1 | 1/34 (2.9%) | 1 | 7/40 (17.5%) | 7 | 8/44 (18.2%) | 8 | 6/45 (13.3%) | 6 |
Infection with normal ANC or Grade 1 or 2 neutrophils::External ear (otitis externa) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia) | 0/1 (0%) | 0 | 4/34 (11.8%) | 4 | 12/40 (30%) | 13 | 24/44 (54.5%) | 24 | 11/45 (24.4%) | 11 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Lymphatic | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Oral cavity-gums (gingivitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Peritoneal cavity | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Pleura (empyema) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Rectum | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 4/40 (10%) | 4 | 4/44 (9.1%) | 4 | 2/45 (4.4%) | 2 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 4 | 3/44 (6.8%) | 3 | 4/45 (8.9%) | 4 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Stomach | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 6/40 (15%) | 6 | 4/44 (9.1%) | 4 | 6/45 (13.3%) | 6 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 4/40 (10%) | 4 | 4/44 (9.1%) | 4 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Wound | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with unknown ANC::Abdomen NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with unknown ANC::Blood | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 2/45 (4.4%) | 2 |
Infection with unknown ANC::Lung (pneumonia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 3/44 (6.8%) | 3 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Meninges (meningitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Sinus | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Upper aerodigestive NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with unknown ANC::Upper airway NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Urinary tract NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Viral hepatitis | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||
Fracture | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 3/44 (6.8%) | 3 | 0/45 (0%) | 0 |
Investigations | ||||||||||
ALT, SGPT (serum glutamic pyruvic transaminase) | 0/1 (0%) | 0 | 5/34 (14.7%) | 10 | 4/40 (10%) | 6 | 16/44 (36.4%) | 25 | 5/45 (11.1%) | 18 |
AST, SGOT(serum glutamic oxaloacetic transaminase) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 4/40 (10%) | 10 | 12/44 (27.3%) | 16 | 1/45 (2.2%) | 2 |
Alkaline phosphatase | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 2 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Amylase | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Carbon monoxide diffusion capacity (DL(co)) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Cardiac troponin I (cTnI) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Creatinine | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 8 | 4/44 (9.1%) | 4 | 0/45 (0%) | 0 |
Leukocytes (total WBC) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Lipase | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Neutrophils/granulocytes (ANC/AGC) | 0/1 (0%) | 0 | 3/34 (8.8%) | 3 | 15/40 (37.5%) | 21 | 13/44 (29.5%) | 20 | 7/45 (15.6%) | 10 |
PTT (Partial Thromboplastin Time) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Platelets | 0/1 (0%) | 0 | 2/34 (5.9%) | 3 | 7/40 (17.5%) | 8 | 7/44 (15.9%) | 18 | 3/45 (6.7%) | 9 |
Prolonged QTc interval | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Weight loss | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||
Acidosis (metabolic or respiratory) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Albumin, serum-low (hypoalbuminemia) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 1/44 (2.3%) | 3 | 0/45 (0%) | 0 |
Alkalosis (metabolic or respiratory) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Anorexia | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Calcium, serum-low (hypocalcemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Dehydration | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Glucose, serum-high (hyperglycemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Glucose, serum-low (hypoglycemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Metabolic/Laboratory - Other (ph>7.5 with life threating consequences ALKALOSIS) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Metabolic/Laboratory - Other (steroid induced hyperglycemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Phosphate, serum-low (hypophosphatemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 5/44 (11.4%) | 7 | 1/45 (2.2%) | 1 |
Potassium, serum-high (hyperkalemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Potassium, serum-low (hypokalemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 3 | 5/44 (11.4%) | 6 | 0/45 (0%) | 0 |
Sodium, serum-low (hyponatremia) | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 2/40 (5%) | 3 | 3/44 (6.8%) | 3 | 0/45 (0%) | 0 |
Triglyceride, serum-high (hypertriglyceridemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Tumor lysis syndrome | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Uric acid, serum-high (hyperuricemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 2 |
Musculoskeletal and connective tissue disorders | ||||||||||
Arthritis (non-septic) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Muscle weakness, generalized or specific area (not due to neuropathy)::Whole body/generalized | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 3/44 (6.8%) | 3 | 1/45 (2.2%) | 1 |
Osteonecrosis (avascular necrosis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Back | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Bone | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Chest wall | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Pain::Neck | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
Secondary Malignancy - | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Secondary Malignancy - possibly related to cancer treatment (squamous cell carcinoma) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Secondary Malignancy - possibly related to cancer treatment | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Nervous system disorders | ||||||||||
Bilirubin (hyperbilirubinemia) | 0/1 (0%) | 0 | 3/34 (8.8%) | 4 | 6/40 (15%) | 7 | 7/44 (15.9%) | 8 | 0/45 (0%) | 0 |
CNS cerebrovascular ischemia | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Cognitive disturbance | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Dizziness | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Edema: head and neck | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Encephalopathy | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 3 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Hemorrhage/Bleeding - Other (Massive Intracranial hemorrhage of left frontal lobe mass) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Leukoencephalopathy (radiographic findings) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Neuropathy: cranial::CN III Pupil, upper eyelid, extra ocular movements | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Neuropathy: cranial::CN VI Lateral deviation of eye | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Neuropathy: motor | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 3/44 (6.8%) | 4 | 0/45 (0%) | 0 |
Neuropathy: sensory | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Pain::Head/headache | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Seizure | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Somnolence/depressed level of consciousness | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Syncope (fainting) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Psychiatric disorders | ||||||||||
Confusion | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Mental status | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Psychosis (hallucinations/delusions) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Renal and urinary disorders | ||||||||||
Cystitis | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Hemorrhage, GU::Urinary NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Renal failure | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 4/40 (10%) | 4 | 5/44 (11.4%) | 5 | 2/45 (4.4%) | 2 |
Stricture/stenosis (including anastomotic), GU::Urethra | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||
Adult Respiratory Distress Syndrome (ARDS) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Apnea | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Cough | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Dyspnea (shortness of breath) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 5/40 (12.5%) | 5 | 3/44 (6.8%) | 3 | 1/45 (2.2%) | 1 |
Edema, larynx | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Hemorrhage, pulmonary/upper respiratory::Bronchopulmonary NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Hemorrhage, pulmonary/upper respiratory::Lung | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Hemorrhage, pulmonary/upper respiratory::Nose | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Hemorrhage/Bleeding - Other (diffuse alveolar hemorrhage) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Hypoxia | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 12/40 (30%) | 13 | 11/44 (25%) | 11 | 3/45 (6.7%) | 3 |
Obstruction/stenosis of airway::Bronchus | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Obstruction/stenosis of airway::Trachea | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Pain::Throat/pharynx/larynx | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Pleural effusion (non-malignant) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 5/44 (11.4%) | 5 | 1/45 (2.2%) | 1 |
Pneumonitis/pulmonary infiltrates | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 6/40 (15%) | 6 | 5/44 (11.4%) | 5 | 0/45 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||
Dermatology/Skin - Other | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pruritus/itching | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Rash/desquamation | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 11/40 (27.5%) | 11 | 9/44 (20.5%) | 9 | 4/45 (8.9%) | 4 |
Rash: acne/acneiform | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Vascular disorders | ||||||||||
Acute vascular leak syndrome | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Hypertension | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 6/40 (15%) | 7 | 3/44 (6.8%) | 3 | 0/45 (0%) | 0 |
Hypotension | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 6/40 (15%) | 6 | 2/44 (4.5%) | 2 | 1/45 (2.2%) | 1 |
Thrombosis/embolism (vascular access-related) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 4/44 (9.1%) | 4 | 1/45 (2.2%) | 1 |
Thrombosis/thrombus/embolism | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 3/44 (6.8%) | 3 | 1/45 (2.2%) | 1 |
Vasculitis | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
Arm IVD Cohort 1 (Th2 DLI) | Arm IVD Cohort 3 (Multiple Th2 DLI) | Arm IVA (12-day Expanded Th2 DLI) | Arm IVB (6-day Expanded Th2 DLI) | Arm IVC (6-day Expanded Th2 DLI and High Dose Sirolimus) | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/1 (100%) | 28/34 (82.4%) | 40/40 (100%) | 38/44 (86.4%) | 36/45 (80%) | |||||
Blood and lymphatic system disorders | ||||||||||
Edema: limb | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 3 | 1/44 (2.3%) | 1 | 3/45 (6.7%) | 3 |
Febrile neutropenia | 0/1 (0%) | 0 | 5/34 (14.7%) | 9 | 1/40 (2.5%) | 1 | 3/44 (6.8%) | 3 | 4/45 (8.9%) | 4 |
Fibrinogen | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Hemoglobin | 0/1 (0%) | 0 | 14/34 (41.2%) | 24 | 34/40 (85%) | 112 | 27/44 (61.4%) | 53 | 18/45 (40%) | 36 |
Lymphedema-related fibrosis | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Lymphopenia | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 6/40 (15%) | 25 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Cardiac disorders | ||||||||||
Left ventricular systolic dysfunction | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Ear and labyrinth disorders | ||||||||||
Thyroid function, low (hypothyroidism) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Endocrine disorders | ||||||||||
Hot flashes/flushes | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pancreatic endocrine: glucose intolerance | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 2/44 (4.5%) | 2 | 1/45 (2.2%) | 1 |
Eye disorders | ||||||||||
Dry eye syndrome | 0/1 (0%) | 0 | 4/34 (11.8%) | 4 | 7/40 (17.5%) | 7 | 4/44 (9.1%) | 4 | 5/45 (11.1%) | 5 |
Eyelid dysfunction | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Hemorrhage, GI::Colon | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Keratitis (corneal inflammation/corneal ulceration) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ocular surface disease | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 3 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ocular/Visual - Other (GVHD Gd 1) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ocular/Visual - Other (Occular GVHD) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Ocular/Visual - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Ocular/Visual - Other (red and itchy eyes) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Taste alteration (dysgeusia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Gastrointestinal disorders | ||||||||||
Ascites (non-malignant) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Colitis | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Colitis, infectious (e.g., Clostridium difficile) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Diarrhea | 0/1 (0%) | 0 | 5/34 (14.7%) | 8 | 9/40 (22.5%) | 9 | 6/44 (13.6%) | 6 | 13/45 (28.9%) | 13 |
Distension/bloating, abdominal | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Dry mouth/salivary gland (xerostomia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 7/45 (15.6%) | 7 |
Dysphagia (difficulty swallowing) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 4/40 (10%) | 4 | 3/44 (6.8%) | 3 | 4/45 (8.9%) | 4 |
Hemorrhage, GI::Lower GI NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Mucositis/stomatitis (clinical exam)::Large bowel | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Mucositis/stomatitis (clinical exam)::Oral cavity | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 12/40 (30%) | 12 | 4/44 (9.1%) | 4 | 3/45 (6.7%) | 3 |
Mucositis/stomatitis (functional/symptomatic)::Large bowel | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Mucositis/stomatitis (functional/symptomatic)::Oral cavity | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Nausea | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 4/40 (10%) | 4 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Pain::Dental/teeth/peridontal | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Esophagus | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 3/44 (6.8%) | 3 | 0/45 (0%) | 0 |
Pain::Oral cavity | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Pain::Oral-gums | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Rigors/chills | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Vomiting | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 2/44 (4.5%) | 2 | 3/45 (6.7%) | 3 |
General disorders | ||||||||||
Fatigue (asthenia, lethargy, malaise) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 9/40 (22.5%) | 12 | 10/44 (22.7%) | 10 | 1/45 (2.2%) | 1 |
Insomnia | 0/1 (0%) | 0 | 1/34 (2.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain - Other (jaw/scalp) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Abdomen NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 2 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Hepatobiliary disorders | ||||||||||
Cholecystitis | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Immune system disorders | ||||||||||
Allergic reaction/hypersensitivity (including drug fever) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infections and infestations | ||||||||||
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection (documented clinically or microbiologically) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 2/45 (4.4%) | 2 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 3 | 0/44 (0%) | 3 | 0/45 (0%) | 0 |
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 3/44 (6.8%) | 3 | 1/45 (2.2%) | 1 |
Infection (documented clinically or microbiologically) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection (documented clinically or microbiologically) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 3/45 (6.7%) | 3 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection | 0/1 (0%) | 0 | 1/34 (2.9%) | 2 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 4/45 (8.9%) | 4 |
Infection | 0/1 (0%) | 0 | 2/34 (5.9%) | 3 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Infection - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection - Other (CMV reactivation) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection - Other (Possible bronchiolitis obliterans) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection - Other (Right arm pain and swelling-catheter celulitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection - Other (Sinusitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection - Other (Stool cultures 5/31: Yersinia, Novovirus as well as H. nana. | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Bladder (urinary) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Blood | 0/1 (0%) | 0 | 15/34 (44.1%) | 19 | 7/40 (17.5%) | 7 | 10/44 (22.7%) | 11 | 14/45 (31.1%) | 14 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Brain (encephalitis, infectious) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Catheter-related | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Colon | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 1/44 (2.3%) | 1 | 4/45 (8.9%) | 4 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Conjunctiva | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Dental-tooth | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Eye NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia) | 0/1 (0%) | 0 | 5/34 (14.7%) | 6 | 4/40 (10%) | 4 | 7/44 (15.9%) | 7 | 10/45 (22.2%) | 10 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Middle ear (otitis media) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Mucosa | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 3/44 (6.8%) | 3 | 4/45 (8.9%) | 4 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Nerve-peripheral | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Nose | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 3/45 (6.7%) | 3 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Oral cavity-gums (gingivitis) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Paranasal | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Pelvis NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Penis | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Peritoneal cavity | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 5/40 (12.5%) | 5 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Rectum | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Salivary gland | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus | 1/1 (100%) | 1 | 2/34 (5.9%) | 2 | 3/40 (7.5%) | 3 | 5/44 (11.4%) | 6 | 4/45 (8.9%) | 4 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis) | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 2/40 (5%) | 2 | 2/44 (4.5%) | 2 | 3/45 (6.7%) | 3 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Stomach | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS | 0/1 (0%) | 0 | 12/34 (35.3%) | 14 | 9/40 (22.5%) | 11 | 17/44 (38.6%) | 17 | 26/45 (57.8%) | 26 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS | 0/1 (0%) | 0 | 9/34 (26.5%) | 9 | 11/40 (27.5%) | 11 | 5/44 (11.4%) | 5 | 10/45 (22.2%) | 10 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Vagina | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with normal ANC or Grade 1 or 2 neutrophils::Wound | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 3/40 (7.5%) | 3 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with unknown ANC::Bladder (urinary) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Infection with unknown ANC::Lung (pneumonia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Mucosa | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Infection with unknown ANC::Sinus | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Infection with unknown ANC::Skin (cellulitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Upper airway NOS | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 3/44 (6.8%) | 3 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Urinary tract NOS | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Infection with unknown ANC::Vagina | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||
Fracture | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Investigations | ||||||||||
ALT, SGPT (serum glutamic pyruvic transaminase) | 1/1 (100%) | 1 | 17/34 (50%) | 38 | 34/40 (85%) | 53 | 29/44 (65.9%) | 81 | 36/45 (80%) | 78 |
AST, SGOT(serum glutamic oxaloacetic transaminase) | 0/1 (0%) | 0 | 12/34 (35.3%) | 17 | 24/40 (60%) | 43 | 20/44 (45.5%) | 27 | 24/45 (53.3%) | 57 |
Alkaline phosphatase | 0/1 (0%) | 0 | 4/34 (11.8%) | 5 | 2/40 (5%) | 2 | 3/44 (6.8%) | 3 | 1/45 (2.2%) | 1 |
Amylase | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Carbon monoxide diffusion capacity (DL(co)) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Cardiac troponin I (cTnI) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Creatinine | 0/1 (0%) | 0 | 1/34 (2.9%) | 2 | 3/40 (7.5%) | 3 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Leukocytes (total WBC) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 6/40 (15%) | 12 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Lipase | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Neutrophils/granulocytes (ANC/AGC) | 0/1 (0%) | 0 | 7/34 (20.6%) | 8 | 40/40 (100%) | 136 | 37/44 (84.1%) | 64 | 26/45 (57.8%) | 44 |
PTT (Partial Thromboplastin Time) | 0/1 (0%) | 0 | 5/34 (14.7%) | 8 | 10/40 (25%) | 12 | 9/44 (20.5%) | 10 | 9/45 (20%) | 10 |
Platelets | 0/1 (0%) | 0 | 7/34 (20.6%) | 10 | 28/40 (70%) | 77 | 18/44 (40.9%) | 33 | 23/45 (51.1%) | 41 |
Prolonged QTc interval | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Sodium, serum-high (hypernatremia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Triglyceride, serum-high (hypertriglyceridemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Weight loss | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||
Albumin, serum-low (hypoalbuminemia) | 0/1 (0%) | 0 | 6/34 (17.6%) | 10 | 10/40 (25%) | 26 | 5/44 (11.4%) | 7 | 9/45 (20%) | 13 |
Alkalosis (metabolic or respiratory) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Anorexia | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
CPK (creatine phosphokinase) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Calcium, serum-high (hypercalcemia) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 2 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Calcium, serum-low (hypocalcemia) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
GGT (gamma-Glutamyl transpeptidase) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 3 | 1/45 (2.2%) | 1 |
Glucose, serum-high (hyperglycemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Magnesium, serum-high (hypermagnesemia) | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 9/40 (22.5%) | 15 | 16/44 (36.4%) | 23 | 6/45 (13.3%) | 7 |
Magnesium, serum-low (hypomagnesemia) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 3/44 (6.8%) | 6 | 1/45 (2.2%) | 1 |
Phosphate, serum-low (hypophosphatemia) | 0/1 (0%) | 0 | 5/34 (14.7%) | 6 | 17/40 (42.5%) | 39 | 16/44 (36.4%) | 30 | 19/45 (42.2%) | 34 |
Potassium, serum-high (hyperkalemia) | 0/1 (0%) | 0 | 5/34 (14.7%) | 8 | 5/40 (12.5%) | 7 | 3/44 (6.8%) | 3 | 5/45 (11.1%) | 7 |
Potassium, serum-low (hypokalemia) | 0/1 (0%) | 0 | 7/34 (20.6%) | 7 | 16/40 (40%) | 32 | 10/44 (22.7%) | 19 | 14/45 (31.1%) | 21 |
Sodium, serum-low (hyponatremia) | 0/1 (0%) | 0 | 3/34 (8.8%) | 3 | 11/40 (27.5%) | 17 | 4/44 (9.1%) | 5 | 2/45 (4.4%) | 2 |
Tumor lysis syndrome | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Uric acid, serum-high (hyperuricemia) | 0/1 (0%) | 0 | 4/34 (11.8%) | 5 | 4/40 (10%) | 8 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Musculoskeletal and connective tissue disorders | ||||||||||
Arthritis (non-septic) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 4/40 (10%) | 4 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Muscle weakness, generalized or specific area (not due to neuropathy)::Extremity-upper | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Myositis (inflammation/damage of muscle) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Pain::Back | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Pain::Bone | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Pain::Chest/thorax NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Joint | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Muscle | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pain::Neck | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 3 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Nervous system disorders | ||||||||||
Bilirubin (hyperbilirubinemia) | 0/1 (0%) | 0 | 8/34 (23.5%) | 15 | 7/40 (17.5%) | 13 | 15/44 (34.1%) | 24 | 14/45 (31.1%) | 35 |
Leukoencephalopathy (radiographic findings) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Mental status | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Mood alteration::Agitation | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Mood alteration::Anxiety | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Neuropathy: sensory | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 3/40 (7.5%) | 3 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Pain::Head/headache | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Seizure | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Syncope (fainting) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Psychiatric disorders | ||||||||||
Confusion | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Renal and urinary disorders | ||||||||||
Cystitis | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 3/45 (6.7%) | 3 |
Hemorrhage, GU::Bladder | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Hemorrhage, GU::Urinary NOS | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Renal/Genitourinary - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Urinary frequency/urgency | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Reproductive system and breast disorders | ||||||||||
Gynecomastia | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Sexual/Reproductive Function - Other (Specify, __) | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Sexual/Reproductive Function - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Vaginal discharge (non-infectious) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Vaginal dryness | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Vaginal mucositis | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Vaginitis (not due to infection) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 2/40 (5%) | 2 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||
Cough | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 3/40 (7.5%) | 3 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Dyspnea (shortness of breath) | 0/1 (0%) | 0 | 3/34 (8.8%) | 3 | 2/40 (5%) | 2 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
FEV(1) | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Hemorrhage, pulmonary/upper respiratory::Nose | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Hyperpigmentation | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 2/44 (4.5%) | 2 | 0/45 (0%) | 0 |
Hypoxia | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Induration/fibrosis (skin and subcutaneous tissue) | 0/1 (0%) | 0 | 2/34 (5.9%) | 2 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 2/45 (4.4%) | 2 |
Pleural effusion (non-malignant) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Pneumonitis/pulmonary infiltrates | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 2/45 (4.4%) | 2 |
Pulmonary/Upper Respiratory - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||
Cytokine release syndrome/acute infusion reaction | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Dermatology/Skin - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Dermatology/Skin - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Dermatology/Skin - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Dermatology/Skin - Other (Specify, __) | 0/1 (0%) | 0 | 1/34 (2.9%) | 2 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Dermatology/Skin - Other (Specify, __) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Dry skin | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 0/40 (0%) | 0 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Hypopigmentation | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Pruritus/itching | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 5/40 (12.5%) | 5 | 2/44 (4.5%) | 2 | 2/45 (4.4%) | 2 |
Rash/desquamation | 0/1 (0%) | 0 | 5/34 (14.7%) | 5 | 30/40 (75%) | 30 | 17/44 (38.6%) | 17 | 18/45 (40%) | 18 |
Rash: acne/acneiform | 0/1 (0%) | 0 | 3/34 (8.8%) | 4 | 0/40 (0%) | 0 | 2/44 (4.5%) | 2 | 2/45 (4.4%) | 2 |
Vascular disorders | ||||||||||
Hypertension | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 5/40 (12.5%) | 5 | 1/44 (2.3%) | 1 | 1/45 (2.2%) | 1 |
Hypotension | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Phlebitis (including superficial thrombosis) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 1/45 (2.2%) | 1 |
Thrombosis/embolism (vascular access-related) | 0/1 (0%) | 0 | 0/34 (0%) | 0 | 1/40 (2.5%) | 1 | 0/44 (0%) | 0 | 0/45 (0%) | 0 |
Thrombosis/thrombus/embolism | 0/1 (0%) | 0 | 1/34 (2.9%) | 1 | 1/40 (2.5%) | 1 | 1/44 (2.3%) | 1 | 0/45 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Steven Pavletic |
---|---|
Organization | National Cancer Institute |
Phone | 301-402-4899 |
steven_pavletic@nih.gov |
- 040055
- 04-C-0055
- NCT00077480