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LBH589 Plus Decitabine for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT00691938
Collaborator
(none)
52
Enrollment
1
Location
7
Arms
74
Duration (Months)
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate the combination of LBH589 and decitabine in patients age ≥ 60 years with high risk Myelodysplastic Syndrome (IPSS Int-2 or High) or Acute Myeloid Leukemia.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

To address the need for less toxic, more effective treatments for older patients with advanced MDS and AML, the purpose of this Phase 1-2 single institution study is to evaluate the safety and efficacy of LBH 589 and decitabine administered in combination.

Decitabine is an epigenetic modifier of gene expression that has been shown to be well-tolerated in this population at the dose schedule proposed in this study, with reasonable efficacy. Although its precise mechanism of action is incompletely understood, it is postulated to work by reactivating the expression of key tumor suppressor genes silenced in tumor cells by reversing a pattern of hypermethylation of promotor elements.

LBH389 is likewise an epigenetic modifier that inhibits the deacetylation of both histones and non-histone proteins, including HSP90 and p53. Although clinical experience with LBH589 in AML is limited, aberrant histone deacetylase activity has been previously shown to play a significant role in the pathogenesis of AML. The addition of LBH589 to a decitabine regimen of previously established efficacy and tolerability will allow us to evaluate the hypothesis that two epigenetic modifiers that are believed to work through distinct mechanisms of action may act together to improve the responses of patients treated with decitabine alone, without significant additional toxicity.

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Study of LBH589 Plus Decitabine for Patients Age ≥ 60 Years With High Risk MDS or AML
Study Start Date :
Jun 1, 2008
Actual Primary Completion Date :
Jul 1, 2013
Actual Study Completion Date :
Aug 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Level 1

LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.

Drug: LBH589
Other Names:
  • Panobinostat

    • Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine

    		•
    Experimental: Level 2

    LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.

    Drug: LBH589
    Other Names:
  • Panobinostat

    • Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine

    		•
    Experimental: Level 3

    LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.

    Drug: LBH589
    Other Names:
  • Panobinostat

    • Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine

    		•
    Experimental: Level 4

    LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.

    Drug: LBH589
    Other Names:
  • Panobinostat

    • Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine

    		•
    Experimental: Level 5

    LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.

    Drug: LBH589
    Other Names:
  • Panobinostat

    • Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine

    		•
    Experimental: Level 5B

    LBH589 40 mg/day three times a week on nonconsecutive days for the first 2 weeks in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.

    Drug: LBH589
    Other Names:
  • Panobinostat

    • Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine

    		•
    Experimental: Phase II

    LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.

    Drug: LBH589
    Other Names:
  • Panobinostat

    • Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase I: Maximum Tolerated Dose (MTD) of LBH589 When Given in Combination With Decitabine [Completion of Phase I enrollment for MTD (approximately 26 months)]

    2. Phase II: Overall Rate of Morphologic Complete Remission (CR) + Cytogenetic Complete Remission (CRc) + Morphologic Complete Remission With Incomplete Blood Count Recovery (CRi) [Up to 12 months]

      Morphologic complete remission (CR). A CR designation requires that the patient achieve the morphologic leukemia-free state with less than 5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods or persistence of extramedullary disease. Patients must also have an absolute neutrophil count of more than 1,000/μLand platelets of 100,000/μL. Cytogenetic complete remission (CRc). A CRc will be defined by the achievement of a CR with reversion to a normal karyotype in a minimum of 20 metaphases analyzed by cytogenetics. Morphologic complete remission with incomplete blood count recovery (CRi): Achievement of all of the criteria for CR except for residual neutropenia (< 1,000/μL) or thrombocytopenia (< 100,000/μL).

    Secondary Outcome Measures

    1. Rate of Cytogenetic Complete Remission (CRc) [Up to 12 months]

      Cytogenetic complete remission (CRc). A CRc will be defined by the achievement of a CR with reversion to a normal karyotype in a minimum of 20 metaphases analyzed by cytogenetics.

    2. Changes in Quality of Life Scores as Measured by the Function Assessment of Cancer Therapy-Leukemia (FACT-Leu) Version 4 [Up to approximately 12 months after start of treatment]

      -The FACT-Leu consists of a 27-item compilation of general questions divided into four primary quality of life domains: physical well-being, social/family well being, emotional well-being, and functional well-being along with a 17 item subscale developed specifically for patients with leukemia.

    3. Time to Response [Up to 12 months]

      Time to response is defined as the date of the first dose of study drug to the date that all criteria for CR or CRi are fulfilled.

    4. Safety and Tolerability of Regimen as Measured by the Rate of the Most Common Adverse Events Experienced [Up to 13 months after start of treatment]

      Adverse events will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0.

    5. Remission Duration [Completion of follow-up (median follow-up was 58 months)]

      Defined as the first date that all criteria for CR, CRi or HI are fulfilled to the date of treatment failure, relapse from CR, or death due to any cause.

    6. Progression-free Survival [Completion of follow-up (median follow-up was 58 months)]

    7. Event-free Survival [Completion of follow-up (median follow-up was 58 months)]

      Event-free survival is defined as the interval from the date of first dose of study drug to date of treatment failure, relapse from CR, or death due to any cause.

    8. Overall Survival [Completion of follow-up (median follow-up was 58 months)]

      Overall survival is defined as the date of first dose of study drug to the date of death from any cause.

    9. Rates of Morphologic Complete Remission With Incomplete Count Recovery (CRi) [Up to 12 months]

      Morphologic complete remission with incomplete blood count recovery (CRi): Achievement of all of the criteria for CR except for residual neutropenia (< 1,000/μL) or thrombocytopenia (< 100,000/μL).

    10. Rate of Hematologic Improvement. [Up to 12 months]

      -Hematologic improvement (HI). Includes the following categories: Erythroid response: Hemoglobin increase by ≥ 1.5 g/dL over baseline in which the pretreatment hemoglobin is < 11 g/dL or reduction of RBC transfusions of at least 4 RBC transfusions / 8 wk compared with the pretreatment transfusion number in the previous 8 weeks. Platelet response. Absolute increase of > 30 x 10^9/L for patients starting with 20 x 10^9/L or increase from < 20 x 10^9/L to > 20 x 109/L and by at least 100% Neutrophil response. At least 100% increase and an absolute increase > 0.5 x 109/L for patients with pretreatment neutrophils < 1.0 x 109/L)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • AML (except t(15;17), inv(16) or t(8;21) and variants) or high risk MDS (IPSS Int-2 or High) diagnosed according to WHO criteria (see Appendix 1)

    • Age ≥ 60 years old

    • Not a candidate for allogeneic stem cell transplantation within next 12 weeks

    • Ability to provide written informed consent, obtained prior to participation in the study and any related procedures being performed

    • Patients must meet the following laboratory criteria:

    • Serum albumin ≥ 3 g/dL

    • Aspartate aminotransferase (AST)/SGOT and alanine aminotransferase (ALT)/SGPT ≤ 2.5 x upper limit of normal (ULN) ) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement

    • Serum bilirubin ≤ 1.5 x ULN

    • Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min

    • Serum potassium ≥ lower limit of normal (LLN)

    • Serum phosphorus ≥ LLN

    • Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN

    • Serum magnesium ≥ LLN, thyroid stimulating hormone (TSH) and free thyroxine (T4) within normal limits (WNL) (patients may be on thyroid hormone replacement)

    • Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal.

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

    Exclusion Criteria:

    • Prior treatment for MDS / AML with Histone deacetylase (HDAC) inhibitor or hypomethylating agent (e.g., Decitabine, azacitidine etc.)

    • Active central nervous system (CNS) involvement with MDS/AML

    • Impaired cardiac function including any one of the following:

    • Screening electrocardiogram (ECG) with a QTc > 450 msec confirmed by central laboratory prior to enrollment to the study

    • Patients with congenital long QT syndrome

    • History of sustained ventricular tachycardia

    • Any history of ventricular fibrillation or torsades de pointes

    • Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.

    • Patients with a myocardial infarction or unstable angina within 6 months of study entry

    • Congestive heart failure (NY Heart Association class III or IV)

    • Right bundle branch block and left anterior hemiblock (bifasicular block)

    • Uncontrolled hypertension

    • Concomitant use of drugs with a risk of causing torsades de pointes

    • Patients with unresolved diarrhea > CTCAE grade 1

    • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589

    • Other concurrent severe and/or uncontrolled medical conditions

    • Patients who have received chemotherapy or any investigational drug < 2 weeks or hydroxyurea < 48 hours prior to starting study drug or who have not recovered from side effects of such therapy.

    • Concomitant use of any anti-cancer therapy or radiation therapy

    • Male patients whose sexual partners are women of child bearing potential (WOCBP) not using effective birth control

    • Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required

    • Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent

    • Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment

    • Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies

    • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University St. Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Geoffrey Uy, M.D., Washington Univerisity

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT00691938
    Other Study ID Numbers:
    • 08-0172 / 201012979
    First Posted:
    Jun 6, 2008
    Last Update Posted:
    Oct 13, 2016
    Last Verified:
    Aug 1, 2016
    Keywords provided by Washington University School of Medicine
    LBH589
    Decitabine
    panobinostat
    histone deacetylase
    methylation
    hypomethylation
    Additional relevant MeSH terms:
    Leukemia
    Preleukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Myelodysplastic Syndromes
    Syndrome
    Decitabine
    Panobinostat

    Study Results

    Participant Flow

    Recruitment Details The study opened to participant enrollment on 06/23/2008 and closed to participant enrollment on 11/06/2012.
    Pre-assignment Detail
    Arm/Group Title Level 1 Level 2 Level 3 Level 4 Level 5 Level 5B Phase II
    Arm/Group Description LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 40 mg/day three times a week on nonconsecutive days for the first 2 weeks in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle.
    Period Title: Overall Study
    STARTED 5 3 6 8 10 6 14
    COMPLETED 4 3 6 8 10 6 14
    NOT COMPLETED 1 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Level 1 Level 2 Level 3 Level 4 Level 5 Level 5B Phase II Total
    Arm/Group Description LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 40 mg/day three times a week on nonconsecutive days for the first 2 weeks in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. Total of all reporting groups
    Overall Participants 5 3 6 8 10 6 14 52
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    69
    69
    68
    72
    73
    71
    66
    70
    Sex: Female, Male (Count of Participants)
    Female
    3
    60%
    1
    33.3%
    3
    50%
    3
    37.5%
    2
    20%
    5
    83.3%
    10
    71.4%
    27
    51.9%
    Male
    2
    40%
    2
    66.7%
    3
    50%
    5
    62.5%
    8
    80%
    1
    16.7%
    4
    28.6%
    25
    48.1%
    Region of Enrollment (participants) [Number]
    United States
    5
    100%
    3
    100%
    6
    100%
    8
    100%
    10
    100%
    6
    100%
    14
    100%
    52
    100%

    Outcome Measures

    1. Primary Outcome
    Title Phase I: Maximum Tolerated Dose (MTD) of LBH589 When Given in Combination With Decitabine
    Description
    Time Frame Completion of Phase I enrollment for MTD (approximately 26 months)

    Outcome Measure Data

    Analysis Population Description
    After enrolling all Phase I patients in Dose Levels 1-5b, the maximum tolerated dose was not determined. The Phase II portion of the study used the 5b dose level.
    Arm/Group Title Phase I (Includes Levels 1-5)
    Arm/Group Description
    Measure Participants 37
    Number [mg (level 5b dosing schedule)]
    40
    2. Primary Outcome
    Title Phase II: Overall Rate of Morphologic Complete Remission (CR) + Cytogenetic Complete Remission (CRc) + Morphologic Complete Remission With Incomplete Blood Count Recovery (CRi)
    Description Morphologic complete remission (CR). A CR designation requires that the patient achieve the morphologic leukemia-free state with less than 5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods or persistence of extramedullary disease. Patients must also have an absolute neutrophil count of more than 1,000/μLand platelets of 100,000/μL. Cytogenetic complete remission (CRc). A CRc will be defined by the achievement of a CR with reversion to a normal karyotype in a minimum of 20 metaphases analyzed by cytogenetics. Morphologic complete remission with incomplete blood count recovery (CRi): Achievement of all of the criteria for CR except for residual neutropenia (< 1,000/μL) or thrombocytopenia (< 100,000/μL).
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 51
    Number [percentage of participants]
    11.8
    236%
    3. Secondary Outcome
    Title Rate of Cytogenetic Complete Remission (CRc)
    Description Cytogenetic complete remission (CRc). A CRc will be defined by the achievement of a CR with reversion to a normal karyotype in a minimum of 20 metaphases analyzed by cytogenetics.
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 51
    Number [percentage of participants]
    3.9
    78%
    4. Secondary Outcome
    Title Changes in Quality of Life Scores as Measured by the Function Assessment of Cancer Therapy-Leukemia (FACT-Leu) Version 4
    Description -The FACT-Leu consists of a 27-item compilation of general questions divided into four primary quality of life domains: physical well-being, social/family well being, emotional well-being, and functional well-being along with a 17 item subscale developed specifically for patients with leukemia.
    Time Frame Up to approximately 12 months after start of treatment

    Outcome Measure Data

    Analysis Population Description
    Data was not collected for this outcome measure.
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 0
    5. Secondary Outcome
    Title Time to Response
    Description Time to response is defined as the date of the first dose of study drug to the date that all criteria for CR or CRi are fulfilled.
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed are participants that met the criteria for CR or CRi.
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 6
    Median (Full Range) [days]
    91.5
    6. Secondary Outcome
    Title Safety and Tolerability of Regimen as Measured by the Rate of the Most Common Adverse Events Experienced
    Description Adverse events will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0.
    Time Frame Up to 13 months after start of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 51
    Fatigue
    88
    1760%
    Febrile neutropenia
    76
    1520%
    Diarrhea
    75
    1500%
    Nausea
    69
    1380%
    7. Secondary Outcome
    Title Remission Duration
    Description Defined as the first date that all criteria for CR, CRi or HI are fulfilled to the date of treatment failure, relapse from CR, or death due to any cause.
    Time Frame Completion of follow-up (median follow-up was 58 months)

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed include those participants who met the criteria for CR, CRi, or HI.
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 7
    Median (Full Range) [days]
    361
    8. Secondary Outcome
    Title Progression-free Survival
    Description
    Time Frame Completion of follow-up (median follow-up was 58 months)

    Outcome Measure Data

    Analysis Population Description
    Data was not collected for this outcome measure. Progression is very hard to define for MDS and AML and including it as a pre-specified secondary outcome measure in the protocol was an oversight.
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 0
    9. Secondary Outcome
    Title Event-free Survival
    Description Event-free survival is defined as the interval from the date of first dose of study drug to date of treatment failure, relapse from CR, or death due to any cause.
    Time Frame Completion of follow-up (median follow-up was 58 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 51
    Median (95% Confidence Interval) [days]
    104
    10. Secondary Outcome
    Title Overall Survival
    Description Overall survival is defined as the date of first dose of study drug to the date of death from any cause.
    Time Frame Completion of follow-up (median follow-up was 58 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 51
    Median (Full Range) [months]
    6.44
    11. Secondary Outcome
    Title Rates of Morphologic Complete Remission With Incomplete Count Recovery (CRi)
    Description Morphologic complete remission with incomplete blood count recovery (CRi): Achievement of all of the criteria for CR except for residual neutropenia (< 1,000/μL) or thrombocytopenia (< 100,000/μL).
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 51
    Number [percentage of participants]
    3.9
    78%
    12. Secondary Outcome
    Title Rate of Hematologic Improvement.
    Description -Hematologic improvement (HI). Includes the following categories: Erythroid response: Hemoglobin increase by ≥ 1.5 g/dL over baseline in which the pretreatment hemoglobin is < 11 g/dL or reduction of RBC transfusions of at least 4 RBC transfusions / 8 wk compared with the pretreatment transfusion number in the previous 8 weeks. Platelet response. Absolute increase of > 30 x 10^9/L for patients starting with 20 x 10^9/L or increase from < 20 x 10^9/L to > 20 x 109/L and by at least 100% Neutrophil response. At least 100% increase and an absolute increase > 0.5 x 109/L for patients with pretreatment neutrophils < 1.0 x 109/L)
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1-Phase II (All Patients Enrolled)
    Arm/Group Description Level 1:LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 2:LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 3: LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 4:LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5:LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle. Level 5B/Phase II:LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m^2 IV on days 1-5 in a 28 day cycle.
    Measure Participants 51
    Number [percentage of participants]
    2.0
    40%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Level 1 Level 2 Level 3 Level 4 Level 5 Level 5B Phase II
    Arm/Group Description LBH589 10 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 15 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 20 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 30 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 40 mg/day three times a week on nonconsecutive days in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 40 mg/day three times a week on nonconsecutive days for the first 2 weeks in a 28 day cycle. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle. LBH589 will be given in the dose and in the schedule that was found to work in the Phase I portion which was dose from Level 5B. Decitabine 20 mg/m2 IV on days 1-5 in a 28 day cycle.
    All Cause Mortality
    Level 1 Level 2 Level 3 Level 4 Level 5 Level 5B Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Level 1 Level 2 Level 3 Level 4 Level 5 Level 5B Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Other (Not Including Serious) Adverse Events
    Level 1 Level 2 Level 3 Level 4 Level 5 Level 5B Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 3/3 (100%) 6/6 (100%) 8/8 (100%) 10/10 (100%) 6/6 (100%) 14/14 (100%)
    Blood and lymphatic system disorders
    Disseminated intravascular coagulation 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Hemoglobin 3/4 (75%) 3/3 (100%) 3/6 (50%) 3/8 (37.5%) 1/10 (10%) 4/6 (66.7%) 7/14 (50%)
    Cardiac disorders
    Atrial fibrillation 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 2/8 (25%) 1/10 (10%) 0/6 (0%) 2/14 (14.3%)
    Atrial flutter 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Bradycardia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 1/14 (7.1%)
    Chest pain 2/4 (50%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Electrocardiogram QT corrected interval prolonged 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Global hypokinesis 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Left ventricular hypertrophy 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Palpitations 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Prolonged QTc interval 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Saccular aneurism 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Sinus arrthymia 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Tachycardia 4/4 (100%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 2/14 (14.3%)
    Eye disorders
    Blurred vision 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Conjunctival hemorrhage 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Eye itch 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Eye pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Sclera discoloration blue 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Swollen, irritated eyes 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Bloating 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Constipation 1/4 (25%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Diarrhea 2/4 (50%) 1/3 (33.3%) 2/6 (33.3%) 3/8 (37.5%) 7/10 (70%) 5/6 (83.3%) 5/14 (35.7%)
    Dry mouth 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Dyspepsia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Dysphagia 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Epigastric distress 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Esophagitis 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Flatulence 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    GI bleeding 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 3/6 (50%) 2/14 (14.3%)
    GI upset 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Gastric ulcer 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Hematochezia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Hemorrhoids 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Ileal hemorrhage 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Mouth sores 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Mucositis 2/4 (50%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 2/10 (20%) 2/6 (33.3%) 3/14 (21.4%)
    Nausea 2/4 (50%) 2/3 (66.7%) 2/6 (33.3%) 2/8 (25%) 6/10 (60%) 4/6 (66.7%) 6/14 (42.9%)
    Taste alteration 0/4 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Upper gastrointestinal hemorrhage 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Vomiting 2/4 (50%) 1/3 (33.3%) 3/6 (50%) 1/8 (12.5%) 5/10 (50%) 2/6 (33.3%) 4/14 (28.6%)
    General disorders
    Angioedema 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Asthenia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Bilateral lower extremity edema 0/4 (0%) 0/3 (0%) 0/6 (0%) 4/8 (50%) 5/10 (50%) 0/6 (0%) 0/14 (0%)
    Death NOS 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Dry lips 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Edema 2/4 (50%) 1/3 (33.3%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Edema: limbs 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 2/14 (14.3%)
    Facial edema 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Fatigue 2/4 (50%) 2/3 (66.7%) 2/6 (33.3%) 6/8 (75%) 6/10 (60%) 6/6 (100%) 7/14 (50%)
    Fever 1/4 (25%) 1/3 (33.3%) 2/6 (33.3%) 0/8 (0%) 2/10 (20%) 1/6 (16.7%) 6/14 (42.9%)
    Gait disturbance 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Generalized pain 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Jaw swelling 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Malaise 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Night sweats 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 3/14 (21.4%)
    Peripheral edema 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Rigors/chills 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 1/8 (12.5%) 3/10 (30%) 1/6 (16.7%) 4/14 (28.6%)
    Supraglottal edema 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Hepatobiliary disorders
    Splenomegaly 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Immune system disorders
    Allergic reaction 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Allergic reaction to transfusion 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Infections and infestations
    Aspergillus sinusitis infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Atypical fungal lung infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    C. albacans infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    C. neg staph & E. faecalis infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    C. neg staph & L. buccalis infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Catheter related infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Cellulitis 1/4 (25%) 1/3 (33.3%) 2/6 (33.3%) 2/8 (25%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Citrobacteremia infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Clostridium difficile infection 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 2/10 (20%) 0/6 (0%) 1/14 (7.1%)
    Coag neg staphylococcus infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Coag. negative staph infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Coagulase negative staphlococcus infection 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    E. Coli infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    E. Coli sepsis infection 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    E. Coli urinary tract infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    EBV meningitis infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Enterobacter cloacae infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Enterococcal line infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 3/14 (21.4%)
    Enterococcus infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Febrile neutropenia 2/4 (50%) 1/3 (33.3%) 1/6 (16.7%) 5/8 (62.5%) 7/10 (70%) 3/6 (50%) 4/14 (28.6%)
    Fungal bacteremia/cladosporium infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Fungal pneumonia infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 3/6 (50%) 0/14 (0%)
    Fungal upper respiratory infection 2/4 (50%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Gram negative sepsis infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Gram positive cocci infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    HSV infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Influenza infection 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Klebsiella infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Lung infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 4/14 (28.6%)
    Multifocal pneumonia 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Opportunistic infection NOS 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Oral herpes simplex virus infection 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Oral thrush infection 2/4 (50%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Parainfluenza infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 1/6 (16.7%) 0/14 (0%)
    Penumonitis, C. glabrata 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Pseudomonas bacteremia infection 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Pseudomonas infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Pulmonary aspergillosis infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    S. viridians and g+ cocci infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Sepsis 0/4 (0%) 0/3 (0%) 0/6 (0%) 2/8 (25%) 2/10 (20%) 1/6 (16.7%) 4/14 (28.6%)
    Sepsis syndrome 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Sinusitis 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 2/10 (20%) 0/6 (0%) 0/14 (0%)
    Skin infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Submandibular gland infection 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Urinary tract infection 1/4 (25%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Yeast infection 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Injury, poisoning and procedural complications
    Bruising 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 2/6 (33.3%) 3/14 (21.4%)
    Death due to fall 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Fall 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Left hip fracture pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Investigations
    ALT 2/4 (50%) 2/3 (66.7%) 1/6 (16.7%) 1/8 (12.5%) 1/10 (10%) 2/6 (33.3%) 2/14 (14.3%)
    AST 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 2/6 (33.3%) 2/14 (14.3%)
    Activated partial thromboplastin time prolonged 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Alkaline phosphatase - high 0/4 (0%) 0/3 (0%) 0/6 (0%) 3/8 (37.5%) 1/10 (10%) 0/6 (0%) 4/14 (28.6%)
    Creatinine 2/4 (50%) 2/3 (66.7%) 0/6 (0%) 2/8 (25%) 4/10 (40%) 1/6 (16.7%) 2/14 (14.3%)
    Hyperbilirubinemia 2/4 (50%) 1/3 (33.3%) 2/6 (33.3%) 0/8 (0%) 2/10 (20%) 0/6 (0%) 4/14 (28.6%)
    INR 2/4 (50%) 1/3 (33.3%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Leukocytes 3/4 (75%) 2/3 (66.7%) 2/6 (33.3%) 6/8 (75%) 4/10 (40%) 0/6 (0%) 9/14 (64.3%)
    Lymphopenia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 2/14 (14.3%)
    Neutrophils 1/4 (25%) 1/3 (33.3%) 3/6 (50%) 5/8 (62.5%) 3/10 (30%) 2/6 (33.3%) 5/14 (35.7%)
    PTT 2/4 (50%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 2/10 (20%) 1/6 (16.7%) 0/14 (0%)
    Platelets 4/4 (100%) 2/3 (66.7%) 3/6 (50%) 2/8 (25%) 4/10 (40%) 6/6 (100%) 3/14 (21.4%)
    Weight gain 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Weight loss 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Metabolism and nutrition disorders
    Acidosis 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Anorexia 1/4 (25%) 2/3 (66.7%) 1/6 (16.7%) 2/8 (25%) 5/10 (50%) 2/6 (33.3%) 4/14 (28.6%)
    Dehydration 0/4 (0%) 0/3 (0%) 0/6 (0%) 2/8 (25%) 1/10 (10%) 1/6 (16.7%) 0/14 (0%)
    Hypercalcemia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Hyperglycemia 0/4 (0%) 0/3 (0%) 0/6 (0%) 2/8 (25%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Hyperkalemia 2/4 (50%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 3/14 (21.4%)
    Hypermagnesemia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Hypernatremia 1/4 (25%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 3/14 (21.4%)
    Hypertriglyceridemia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Hypoalbuminemia 2/4 (50%) 2/3 (66.7%) 3/6 (50%) 2/8 (25%) 1/10 (10%) 2/6 (33.3%) 7/14 (50%)
    Hypocalcemia 3/4 (75%) 2/3 (66.7%) 3/6 (50%) 4/8 (50%) 5/10 (50%) 3/6 (50%) 5/14 (35.7%)
    Hypoglycemia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Hypokalemia 2/4 (50%) 2/3 (66.7%) 0/6 (0%) 1/8 (12.5%) 3/10 (30%) 0/6 (0%) 5/14 (35.7%)
    Hypomagnesemia 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Hyponatremia 3/4 (75%) 2/3 (66.7%) 1/6 (16.7%) 1/8 (12.5%) 6/10 (60%) 1/6 (16.7%) 7/14 (50%)
    Hypophosphatemia 2/4 (50%) 1/3 (33.3%) 3/6 (50%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Tumor lysis syndrome 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritic hand pain 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Back pain 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 1/6 (16.7%) 1/14 (7.1%)
    Bilateral hand pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Bone pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Generalized muscle weakness 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 4/8 (50%) 3/10 (30%) 4/6 (66.7%) 3/14 (21.4%)
    Joint range of motion decreased 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Left lower leg joint pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Leg pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Muscle weakness left-sided 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Muscle weakness lower limb 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Myalgia (chest) 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Pain in extremity 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Shoulder pain 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Substernal pain 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Nervous system disorders
    Cognitive disturbance 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Dizziness 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Headache 1/4 (25%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 1/6 (16.7%) 4/14 (28.6%)
    Lightheadedness 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Neuropathy - fingers 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Neuropathy - right chest 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Neuropathy - right foot drop 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Paresthesia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Restless leg syndrome 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Stroke 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Supratentorial ventriculomegaly 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Syncope 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 1/14 (7.1%)
    Tingling left leg 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Psychiatric disorders
    Agitation - mental status change 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Altered mental status 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Anxiety 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Confusion 2/4 (50%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 3/10 (30%) 0/6 (0%) 1/14 (7.1%)
    Depression 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Insomnia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Psychosis - visual hallucinations 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Suicide 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Hematuria 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 2/10 (20%) 0/6 (0%) 2/14 (14.3%)
    Hemoglobinuria 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Proteinuria 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 1/6 (16.7%) 2/14 (14.3%)
    Renal failure 1/4 (25%) 1/3 (33.3%) 0/6 (0%) 2/8 (25%) 2/10 (20%) 0/6 (0%) 0/14 (0%)
    Urinary hesitancy 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Urinary retention 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Urination difficult 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Urine discoloration 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Reproductive system and breast disorders
    Vulvar lesions 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Asthma exacerbation 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 3/14 (21.4%)
    Cough 1/4 (25%) 1/3 (33.3%) 2/6 (33.3%) 2/8 (25%) 5/10 (50%) 2/6 (33.3%) 4/14 (28.6%)
    Dyspnea 1/4 (25%) 0/3 (0%) 1/6 (16.7%) 3/8 (37.5%) 2/10 (20%) 2/6 (33.3%) 5/14 (35.7%)
    Epistaxis 0/4 (0%) 0/3 (0%) 0/6 (0%) 3/8 (37.5%) 0/10 (0%) 0/6 (0%) 4/14 (28.6%)
    Hypoxia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 2/10 (20%) 0/6 (0%) 1/14 (7.1%)
    Pneumonia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 2/14 (14.3%)
    Prolonged intubation 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Pulmonary edema 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Pulmonary nodules 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Respiratory failure 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 2/14 (14.3%)
    Secretions 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Sinus congestion 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Sinus pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Tachypnea 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Throat pain 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Tracheostomy 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Wheezing 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Bronchospasm 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Skin and subcutaneous tissue disorders
    Eccymosis, right arm 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Ecthyma (groin) 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Hair loss/alopecia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Nail changes; dystrophic nails 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Penis erythema 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Perirectal left buttock abscess/ulcer 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Pruritis 0/4 (0%) 0/3 (0%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Rash 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 1/8 (12.5%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Rash, actinoform 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 0/14 (0%)
    Rash, erythema diffuse 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 2/6 (33.3%) 0/14 (0%)
    Rash, macropapular 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 1/10 (10%) 0/6 (0%) 2/14 (14.3%)
    Rash, petechiae 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 3/10 (30%) 0/6 (0%) 0/14 (0%)
    Right lower quadrant abdomen ulcer 0/4 (0%) 1/3 (33.3%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Sore/lesion on buttocks 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Sunburn 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 1/6 (16.7%) 0/14 (0%)
    Dry skin 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Erythema multiforme 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Purpura 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 2/14 (14.3%)
    Skin ulceration 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Petechia 0/4 (0%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 1/14 (7.1%)
    Surgical and medical procedures
    Biopsy site pain 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Incisional pain 1/4 (25%) 0/3 (0%) 0/6 (0%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Vascular disorders
    Hematoma 0/4 (0%) 0/3 (0%) 1/6 (16.7%) 0/8 (0%) 0/10 (0%) 0/6 (0%) 0/14 (0%)
    Hypertension 2/4 (50%) 1/3 (33.3%) 0/6 (0%) 1/8 (12.5%) 1/10 (10%) 0/6 (0%) 1/14 (7.1%)
    Hypotension 1/4 (25%) 1/3 (33.3%) 1/6 (16.7%) 4/8 (50%) 3/10 (30%) 0/6 (0%) 4/14 (28.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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 Geoffrey Uy, M.D.
    Organization Washington University School of Medicine
    Phone 314-454-8304
    Email guy@wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT00691938
    Other Study ID Numbers:
    • 08-0172 / 201012979
    First Posted:
    Jun 6, 2008
    Last Update Posted:
    Oct 13, 2016
    Last Verified:
    Aug 1, 2016