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Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation

Sponsor
Washington University School of Medicine (Other)
Overall Status
Terminated
CT.gov ID
NCT01747499
Collaborator
The Foundation for Barnes-Jewish Hospital (Other), National Cancer Institute (NCI) (NIH), National Institutes of Health (NIH) (NIH)
54
Enrollment
1
Location
5
Arms
68.3
Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this phase I/II study is to define the maximum tolerated dose of 5-AzaC and the effect on grade II-IV GvHD when given after matched unrelated donor transplant (MUD).

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

Study Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Trial of Intravenous Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation
Study Start Date :
Apr 15, 2013
Actual Primary Completion Date :
Aug 31, 2018
Actual Study Completion Date :
Dec 24, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1

Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95

Drug: Azacitidine
Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC

    		•
    Experimental: Cohort 2

    Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95

    Drug: Azacitidine
    Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC

    		•
    Experimental: Cohort 3

    Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95

    Drug: Azacitidine
    Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC

    		•
    Experimental: Cohort 4

    Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95

    Drug: Azacitidine
    Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC

    		•
    Experimental: Phase II Cohort

    Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95

    Drug: Azacitidine
    Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase I: to Determine the Maximum Tolerated Dose (MTD) of Azacitidine in Patients Undergoing Matched (8 Out of 8) Unrelated Donor Transplant for Any Hematological Malignancy in Remission or With Stable Disease. [28 days]

      The MTD is defined as the dose level immediately below the dose level at which patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity.

    2. Phase II: Number of Participants With Grades II-IV Acute GvHD [Day +180]

      GVHD rate and severity will be assessed based on modified Glucksberg criteria. Grade II-IV and III-IV aGVHD in first 180 days after transplant will be assessed.

    Secondary Outcome Measures

    1. Rate of Grades III-IV aGVHD at Day +180. [Day +180]

      GVHD rate and severity will be assessed based on modified Glucksberg criteria.

    2. Overall Survival as Measured by Number of Participants Alive at 1 Year After Transplant [One year after transplant]

      Date of transplant to the date of death from any cause.

    3. Treatment-related Mortality [Day +140]

      Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause.

    4. Number of Participants Who Relapsed Within the First Year of Transplant [Within the first year of transplant]

      Recurrence of the original malignant disease after transplantation. The time to relapse is the time to the first observation of hematologic, radiographic, or cytogenetic changes, which result in characterization as relapse.

    5. Rate of Chronic GvHD [One year after transplant]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.

    • Phase I: Diagnosis of any hematological malignancy listed below (excluding myelofibrosis) in remission or with stable minimal residual disease

    • Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse after any remission

    • Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse after any remission

    • Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System

    • Chronic myelogenous leukemia (CML) in accelerated or second chronic phase

    • Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or refractory relapse

    • Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior regimens

    • Multiple myeloma (MM), Stage 2-3

    • Myeloproliferative disorder or neoplasm

    • Phase II: Diagnosis of AML in remission 1 or 2 or a diagnosis of myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System.

    • Patients with MDS must be transplant candidates by current clinical standards.

    • Patients who have been treated with hypomethylating agents prior to entering the study are eligible.

    • Must have matched unrelated donor (8 of 8 HLA match at A, B, C, and DR loci) by high resolution DNA typing

    • Must have donor peripheral blood stem cells mobilized by NMDP standards. No bone marrow donors.

    • Must have 2-8 x 10^6 CD34+ cells/kg (recipient weight) infused on Day 0.

    • Must have at least one additional aliquot of >=1 x 10^6 CD34/kg cryopreserved cells stored at the time of transplant.

    • Must receive a myeloablative or reduced intensity conditioning regimen for SCT as defined by the CIBMTR

    • Cyclophosphamide and single dose total body irradiation

    • Fludarabine and busulfan

    • Fractionated TBI and cyclophosphamide

    • Busulfan and cyclophosphamide

    • Must be able to receive GVHD prophylaxis with tacrolimus and methotrexate.

    • Must be ≥ 18 yrs old and ≤ 70 yrs old. Azacitidine is not approved by the FDA for use in children.

    • Must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

    • Must have laboratory results indicating:

    • Total bilirubin < 2.0 mg/dl, unless a diagnosis of Gilbert's disease

    • AST/ALT ≤ 3 X the upper limit of institutional normal

    • Serum creatinine ≤ 2.0 mg/dl

    • Patient must have ability to understand and willingness to provide written informed consent prior to participation in the study and any related procedures being performed.

    • The effects of azacitidine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because category D agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing age must have a negative serum pregnancy test (ß-human chorionic gonadotropin) within 72 hours prior to initiating the conditioning regimen and be willing to not become pregnant by using effective contraception while undergoing treatment and for at least 3 months after the last dose of azacitidine.

    • Men must be willing not to father a new child while receiving therapy. They must use an effective barrier method of contraception during the study and for 3 months following the last dose.

    Exclusion Criteria:

    • Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 28 days after transplant.

    • Must not be receiving any other investigational agents within 14 days of first dose of azacitidine (Day 7).

    • Must not have myeloablative conditioning as defined below:

    • TBI < or = Gy +/- purine analog

    • Flu + Cy +/- ATG

    • Flu + AraC + Ida

    • Cladribine + AraC

    • Total Lymphoid Irradiation + ATG

    • Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens. Antithymocyte globulin is excluded due to its potential impact on modulating the incidence of GvHD or GvL.

    • Must not have uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

    • Must not be pregnant or breastfeeding. Pregnant women are excluded from this study because azacitidine is a Category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, breastfeeding should be discontinued if the mother is treated azacitidine. These potential risks may also apply to other agents used in this study.

    • Must not have a known or suspected hypersensitivity to azacitidine, mannitol, or compounds of similar composition to azacitidine..

    • Must not have an advanced malignant hepatic tumor.

    • Must not be HIV, HBV, or HCV positive.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Saint Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine
    • The Foundation for Barnes-Jewish Hospital
    • National Cancer Institute (NCI)
    • National Institutes of Health (NIH)

    Investigators

    • Principal Investigator: Mark A. Schroeder, M.D., Washington University School of Medicine

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT01747499
    Other Study ID Numbers:
    • 201303012
    • 1P50CA171963-01A1
    First Posted:
    Dec 11, 2012
    Last Update Posted:
    Oct 16, 2019
    Last Verified:
    Sep 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Myelodysplastic Syndromes
    Azacitidine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    Period Title: Overall Study
    STARTED 3 3 3 6 39
    COMPLETED 2 2 3 4 24
    NOT COMPLETED 1 1 0 2 15

    Baseline Characteristics

    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort Total
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95 Total of all reporting groups
    Overall Participants 3 3 3 6 39 54
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    46
    57
    63
    58.5
    59
    59
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    2
    66.7%
    0
    0%
    2
    33.3%
    17
    43.6%
    22
    40.7%
    Male
    2
    66.7%
    1
    33.3%
    3
    100%
    4
    66.7%
    22
    56.4%
    32
    59.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    39
    100%
    54
    100%
    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%
    0
    0%
    0
    0%
    1
    16.7%
    1
    2.6%
    2
    3.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.6%
    1
    1.9%
    White
    3
    100%
    3
    100%
    3
    100%
    5
    83.3%
    37
    94.9%
    51
    94.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    39
    100%
    54
    100%

    Outcome Measures

    1. Primary Outcome
    Title Phase I: to Determine the Maximum Tolerated Dose (MTD) of Azacitidine in Patients Undergoing Matched (8 Out of 8) Unrelated Donor Transplant for Any Hematological Malignancy in Remission or With Stable Disease.
    Description The MTD is defined as the dose level immediately below the dose level at which patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity.
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I
    Arm/Group Description Conditioning treatment Transplant on Day 0 Azacitidine Days 7-11 Azacitidine Days 35-39 Azacitidine Days 63-67 Azacitidine Days 91-95
    Measure Participants 15
    Number [mg/m^2]
    45
    2. Primary Outcome
    Title Phase II: Number of Participants With Grades II-IV Acute GvHD
    Description GVHD rate and severity will be assessed based on modified Glucksberg criteria. Grade II-IV and III-IV aGVHD in first 180 days after transplant will be assessed.
    Time Frame Day +180

    Outcome Measure Data

    Analysis Population Description
    One patient was enrolled and treated with 1 cycle but was ultimately ineligible following a laboratory error and is not evaluable for this outcome measure.
    Arm/Group Title Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    Measure Participants 38
    Count of Participants [Participants]
    16
    533.3%
    3. Secondary Outcome
    Title Rate of Grades III-IV aGVHD at Day +180.
    Description GVHD rate and severity will be assessed based on modified Glucksberg criteria.
    Time Frame Day +180

    Outcome Measure Data

    Analysis Population Description
    One patient in Phase II cohort was enrolled and treated with 1 cycle but was ultimately ineligible following a laboratory error and is not evaluable for this outcome measure.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    Measure Participants 3 3 3 6 38
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    23.1%
    4. Secondary Outcome
    Title Overall Survival as Measured by Number of Participants Alive at 1 Year After Transplant
    Description Date of transplant to the date of death from any cause.
    Time Frame One year after transplant

    Outcome Measure Data

    Analysis Population Description
    One patient in Phase II cohort was enrolled and treated with 1 cycle but was ultimately ineligible following a laboratory error and is not evaluable for this outcome measure.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    Measure Participants 3 3 3 6 38
    Count of Participants [Participants]
    3
    100%
    2
    66.7%
    2
    66.7%
    4
    66.7%
    28
    71.8%
    5. Secondary Outcome
    Title Treatment-related Mortality
    Description Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause.
    Time Frame Day +140

    Outcome Measure Data

    Analysis Population Description
    One patient in Phase II cohort was enrolled and treated with 1 cycle but was ultimately ineligible following a laboratory error and is not evaluable for this outcome measure.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    Measure Participants 3 3 3 6 38
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    2
    5.1%
    6. Secondary Outcome
    Title Number of Participants Who Relapsed Within the First Year of Transplant
    Description Recurrence of the original malignant disease after transplantation. The time to relapse is the time to the first observation of hematologic, radiographic, or cytogenetic changes, which result in characterization as relapse.
    Time Frame Within the first year of transplant

    Outcome Measure Data

    Analysis Population Description
    One patient in Phase II cohort was enrolled and treated with 1 cycle but was ultimately ineligible following a laboratory error and is not evaluable for this outcome measure.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    Measure Participants 3 3 3 6 38
    Count of Participants [Participants]
    1
    33.3%
    0
    0%
    1
    33.3%
    1
    16.7%
    4
    10.3%
    7. Secondary Outcome
    Title Rate of Chronic GvHD
    Description
    Time Frame One year after transplant

    Outcome Measure Data

    Analysis Population Description
    One patient in Phase II cohort was enrolled and treated with 1 cycle but was ultimately ineligible following a laboratory error and is not evaluable for this outcome measure.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    Measure Participants 3 3 3 6 38
    Count of Participants [Participants]
    3
    100%
    2
    66.7%
    2
    66.7%
    3
    50%
    27
    69.2%

    Adverse Events

    Time Frame -Adverse events (AEs) were collected from Day +7-Day +140 visit or 30 days after their last dose of azacitidine (for patients that did not complete all 4 cycles of treatment). -All AEs were collected for Phase I patients -Only selected adverse events were collected for Phase II patients *all grade 3, 4, or 5 *any that require azacitidine treatment to be delayed, held, or discontinued *any that require modification of GVHD prophylaxis medications *any grade mucositis and any infection
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Arm/Group Description Conditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95
    All Cause Mortality
    Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 2/6 (33.3%) 12/39 (30.8%)
    Serious Adverse Events
    Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 2/3 (66.7%) 2/3 (66.7%) 3/6 (50%) 23/39 (59%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Gastrointestinal disorders
    Abdominal pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Diarrhea 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 5/39 (12.8%)
    Nausea 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/39 (5.1%)
    General disorders
    Fever 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/39 (7.7%)
    Edema limbs 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Infections and infestations
    Sepsis 0/3 (0%) 0/3 (0%) 0/3 (0%) 3/6 (50%) 1/39 (2.6%)
    Respiratory infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    HHV-6 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Paronychia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Skin infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Lung infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Metabolism and nutrition disorders
    Dehydration 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Hyperkalemia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Relapsed acute leukemia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Nervous system disorders
    Seizure 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Renal and urinary disorders
    Urinary incontinence 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Acute kidney failure 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 6/39 (15.4%)
    Respiratory, thoracic and mediastinal disorders
    Hypoxic respiratory failure 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Hypoxia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Respiratory failure 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Skin and subcutaneous tissue disorders
    Pruritic rash 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Rash maculo-papular 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Vascular disorders
    Hematoma 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Vascular access complication 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Thromboembolic event 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Other (Not Including Serious) Adverse Events
    Cohort 1 Cohort 2 Cohort 3 Cohort 4 Phase II Cohort
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%) 39/39 (100%)
    Blood and lymphatic system disorders
    Anemia 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 5/6 (83.3%) 14/39 (35.9%)
    Febrile neutropenia 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 2/6 (33.3%) 5/39 (12.8%)
    Hemolysis 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/39 (2.6%)
    Hemolytic uremic syndrome 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Cardiac disorders
    Atrial fibrillation 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 2/39 (5.1%)
    Heart failure 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/39 (5.1%)
    Myocardial infarction 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Pericardial effusion 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Sinus tachycardia 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Supraventricular tachycardia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Tachycardia (NOS) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Endocrine disorders
    Cushingoid 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/39 (0%)
    Eye disorders
    Dry eye 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Vision changes (not otherwise specified) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Watering eyes 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Abdominal pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Bloating 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Colitis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Constipation 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 1/6 (16.7%) 0/39 (0%)
    Diarrhea 2/3 (66.7%) 1/3 (33.3%) 2/3 (66.7%) 3/6 (50%) 4/39 (10.3%)
    Dry mouth 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Dyspepsia 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Dysphagia 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Ileus 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Lower gastrointestinal hemorrhage 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 1/39 (2.6%)
    Mouth gumminess 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Mucositis oral 3/3 (100%) 1/3 (33.3%) 1/3 (33.3%) 6/6 (100%) 20/39 (51.3%)
    Nausea 3/3 (100%) 2/3 (66.7%) 2/3 (66.7%) 2/6 (33.3%) 0/39 (0%)
    Oral hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Oral pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Sore in mouth 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Vomiting 3/3 (100%) 2/3 (66.7%) 1/3 (33.3%) 3/6 (50%) 0/39 (0%)
    General disorders
    Chills 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Edema limbs 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 3/6 (50%) 2/39 (5.1%)
    Fatigue 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 4/39 (10.3%)
    Fever 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Flu Like Symptoms 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Localized edema 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Neck edema 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Non-cardiac chest pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 3/39 (7.7%)
    Hepatobiliary disorders
    Hepatic failure 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Immune system disorders
    Allergic reaction 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Infections and infestations
    BK virus 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    C. Difficile 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/39 (5.1%)
    CMV Positive Culture 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    CMV Viremia 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 3/39 (7.7%)
    Catheter related infection 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Coagulase Negative Staphyloccus-Bacteremia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/39 (5.1%)
    Coronavirus OC43 Parainfluenza virus Type 3 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    E. coli bacteremia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Enterocolitis infectious 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Healthcare associated pneumonia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Hepatic infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Influenza A 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Lung infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 2/39 (5.1%)
    Mucosal infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/39 (10.3%)
    Papulopustular rash 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Rhinovirus positive culture 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Sepsis 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Sinusitis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Sinusitis (rhinovirus/enterovirus) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Skin infection 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/39 (2.6%)
    Streptococcus mitis bacteremia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Upper respiratory infection 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/39 (2.6%)
    Urinary tract infection 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/39 (7.7%)
    Injury, poisoning and procedural complications
    Bruising 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Dog bite to finger 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Fall 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Spinal fracture 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Vascular access complication 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 3/6 (50%) 2/39 (5.1%)
    Alanine aminotransferase increased 2/3 (66.7%) 2/3 (66.7%) 3/3 (100%) 4/6 (66.7%) 6/39 (15.4%)
    Alkaline phosphatase increased 0/3 (0%) 2/3 (66.7%) 2/3 (66.7%) 4/6 (66.7%) 0/39 (0%)
    Aspartate aminotransferase increased 2/3 (66.7%) 1/3 (33.3%) 3/3 (100%) 4/6 (66.7%) 2/39 (5.1%)
    Blood bilirubin increased 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 3/6 (50%) 4/39 (10.3%)
    Creatinine increased 0/3 (0%) 1/3 (33.3%) 2/3 (66.7%) 3/6 (50%) 2/39 (5.1%)
    Ejection fracture decreased 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Fibrinogen decreased 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    INR increased 1/3 (33.3%) 3/3 (100%) 0/3 (0%) 5/6 (83.3%) 0/39 (0%)
    Lymphocyte count decreased 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 4/6 (66.7%) 17/39 (43.6%)
    Neutrophil count decreased 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 3/6 (50%) 21/39 (53.8%)
    Platelet count decreased 2/3 (66.7%) 2/3 (66.7%) 1/3 (33.3%) 5/6 (83.3%) 20/39 (51.3%)
    Weight loss 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    White blood cell count decreased 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 5/6 (83.3%) 15/39 (38.5%)
    Metabolism and nutrition disorders
    Acidosis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Alkalosis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Anorexia 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 2/6 (33.3%) 5/39 (12.8%)
    Dehydration 0/3 (0%) 0/3 (0%) 0/3 (0%) 3/6 (50%) 3/39 (7.7%)
    Hyperglycemia 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 3/6 (50%) 12/39 (30.8%)
    Hyperkalemia 1/3 (33.3%) 2/3 (66.7%) 3/3 (100%) 5/6 (83.3%) 2/39 (5.1%)
    Hypermagnesemia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 1/39 (2.6%)
    Hypernatremia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Hyperuricemia 2/3 (66.7%) 0/3 (0%) 2/3 (66.7%) 0/6 (0%) 0/39 (0%)
    Hypoalbuminemia 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 5/6 (83.3%) 1/39 (2.6%)
    Hypocalcemia 1/3 (33.3%) 3/3 (100%) 0/3 (0%) 2/6 (33.3%) 0/39 (0%)
    Hypokalemia 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 4/6 (66.7%) 3/39 (7.7%)
    Hypomagnesemia 2/3 (66.7%) 1/3 (33.3%) 3/3 (100%) 4/6 (66.7%) 0/39 (0%)
    Hyponatremia 2/3 (66.7%) 2/3 (66.7%) 3/3 (100%) 6/6 (100%) 4/39 (10.3%)
    Hypophosphatemia 3/3 (100%) 1/3 (33.3%) 1/3 (33.3%) 5/6 (83.3%) 14/39 (35.9%)
    Iron overload 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/39 (2.6%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/3 (33.3%) 2/3 (66.7%) 0/3 (0%) 2/6 (33.3%) 2/39 (5.1%)
    Bone pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Generalized muscle weakness 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/39 (7.7%)
    Muscle weakness right-sided 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Myalgia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Myopathy 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Neck pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Osteoporosis 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Pain in extremity 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 0/39 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Nervous system disorders
    Dizziness 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Drooling 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Dysarthria 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Encephalopathy 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Facial droop 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Facial muscle weakness 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Headache 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 0/39 (0%)
    Hypersomnia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Lethargy 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Paresthesia 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Peripheral motor neuropathy 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Peripheral sensory neuropathy 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Seizure 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Sinus pain 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Somnolence 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/39 (0%)
    Stroke 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Tremor 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Psychiatric disorders
    Agitation 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Altered mental status 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Anxiety 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/39 (0%)
    Confusion 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 2/6 (33.3%) 0/39 (0%)
    Depression 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Hallucinations 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Insomnia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Restlessness 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 3/6 (50%) 3/39 (7.7%)
    Bladder spasm 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Chronic kidney disease 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Hematuria 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 2/39 (5.1%)
    Proteinuria 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Urinary frequency 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Urinary retention 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Reproductive system and breast disorders
    Perianal pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Vaginal hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute worsening of COPD 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Allergic rhinitis 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Atelectasis 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/39 (2.6%)
    Cough 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/39 (2.6%)
    Dyspnea 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/39 (2.6%)
    Epistaxis 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Hiccups 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Hoarseness 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Hypoxia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Nasal congestion 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Pleural effusion 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Postnasal drip 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Productive cough 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Pulmonary edema 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/39 (2.6%)
    Respiratory failure 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 2/39 (5.1%)
    Sore throat 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/39 (2.6%)
    Wheezing 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Blanching erythema 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Dry skin 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Erythema (face) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Erythema at catheter site 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Hyperhidrosis 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Lip ulcer 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Pruritus 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 2/39 (5.1%)
    Purpura 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Rash (sun burn) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Rash maculo-papular 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 5/6 (83.3%) 10/39 (25.6%)
    Skin hyperpigmentation 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 0/39 (0%)
    Skin ulceration 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/39 (0%)
    Vascular disorders
    Hot flashes 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Hypertension 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/39 (10.3%)
    Hypotension 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 1/39 (2.6%)
    Orthostatic hypotension 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/39 (0%)
    Thromboembolic event 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/39 (0%)

    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 Mark A. Schroeder, M.D.
    Organization Washington University School of Medicine
    Phone 314-454-8304
    Email markschroeder@wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT01747499
    Other Study ID Numbers:
    • 201303012
    • 1P50CA171963-01A1
    First Posted:
    Dec 11, 2012
    Last Update Posted:
    Oct 16, 2019
    Last Verified:
    Sep 1, 2019