Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Sponsor
University of Wisconsin, Madison (Other)
Overall Status
Completed
CT.gov ID
NCT01707004
Collaborator
National Cancer Institute (NCI) (NIH)
20
1
1
52.7
0.4

Study Details

Study Description

Brief Summary

This phase II trial studies how well decitabine and total-body irradiation followed by donor bone marrow transplant and cyclophosphamide works in treating patients with relapsed or refractory acute myeloid leukemia. Giving decitabine and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving decitabine and total-body irradiation before the transplant together with high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil after the transplant may stop this from happening.

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine overall survival at 100 days after transplantation following decitabine and a bone marrow transplant using a donor that is at least partially-matched and a myeloablative preparative regimen with post-transplantation cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis.
SECONDARY OBJECTIVES:
I. Patients enrolled in this study will also be followed for the following endpoints:

neutrophil and platelet recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, incidence of infection, treatment-related mortality, time to relapse/progression, overall survival, and progression-free survival.

OUTLINE:

Beginning between days -29 and -22, patients receive decitabine intravenously (IV) over 1 hour daily for 10 days, fludarabine phosphate IV over 30 minutes on days -5 to -2, and busulfan IV over 3 hours on days -5 to -2.

PREPARATIVE REGIMEN: Patients undergo total-body irradiation twice daily (BID) on day -1.

TRANSPLANT: Patients undergo allogeneic bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus orally (PO) BID or IV continuously on days 5-180, mycophenolate mofetil PO three times daily (TID) on days 5-35 and filgrastim subcutaneously (SC) beginning day 5 until absolute neutrophil count (ANC) >= 1,000/mm^3 for 3 consecutive days.

After completion of study treatment, patients are followed up at 6 months and 1 year.

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Decitabine Followed by Bone Marrow Transplant and High-Dose Cyclophosphamide for the Treatment of Relapsed and Refractory Acute Myeloid Neoplasms
Actual Study Start Date :
May 16, 2013
Actual Primary Completion Date :
Jul 22, 2017
Actual Study Completion Date :
Oct 7, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (donor bone marrow transplant)

Beginning between days -29 and -22, patients receive decitabine IV over 1 hour daily for 10 days, fludarabine phosphate IV over 30 minutes on days -5 to -2, and busulfan IV over 3 hours on days -5 to -2. PREPARATIVE REGIMEN: Patients undergo total-body irradiation BID on day -1. TRANSPLANT: Patients undergo allogeneic bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus PO BID or IV continuously on days 5-180, mycophenolate mofetil PO TID on days 5-35, and filgrastim SC beginning day 5 until ANC >= 1,000/mm^3 for 3 consecutive days.

Drug: decitabine
Given IV
Other Names:
  • 5-aza-2'-deoxycytidine (5-aza-dCyd)
  • 5-azacytidine (5AZA)
  • decitabine (DAC)
  • Drug: fludarabine phosphate
    Given IV
    Other Names:
  • Fludarabine phosphate (2-F-ara-AMP)
  • Beneflur
  • Fludara
  • Drug: busulfan
    Given IV
    Other Names:
  • busulfan (BSF)
  • busulfan (BU)
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Drug: cyclophosphamide
    Given IV
    Other Names:
  • cyclophosphamide (CPM)
  • cyclophosphamide (CTX)
  • Cytoxan
  • Endoxan
  • Endoxana
  • Drug: tacrolimus
    Given PO or IV
    Other Names:
  • tacrolimus (FK 506)
  • Prograf
  • Drug: mycophenolate mofetil
    Given PO
    Other Names:
  • Cellcept
  • mycophenolate mofetil (MMF)
  • Biological: filgrastim
    Given SC
    Other Names:
  • granulocyte-colony stimulating factor (G-CSF)
  • Neupogen
  • Radiation: total-body irradiation
    Undergo total-body irradiation
    Other Names:
  • total body irradiation (TBI)
  • Procedure: allogeneic bone marrow transplantation
    Undergo allogeneic bone marrow transplantation
    Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Day 100]

      Will be analyzed using Kaplan-Meier (KM) method, and OS will be obtained from the KM estimates along with 95% confidence intervals.

    Secondary Outcome Measures

    1. Time to Neutrophil Recovery [Up to 1 year]

      Defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/ul for three consecutive measurements on different days. Will be summarized with mean and standard deviation or median and interquartile range, and the change will be tested using a one-sample paired t-test at a two-tailed significance level of 0.05.

    2. Percentage of Participants With Platelet Recovery by Day 30 [Up to day 30]

      Platelet recovery is defined as the first day of a platelet count greater than 20,000/mm^3 with no platelet transfusions. Will be summarized with mean and standard deviation or median and interquartile range, and the change will be tested using a one-sample paired t-test at a two-tailed significance level of 0.05.

    3. Number of Participants With Primary Graft Failure [Day 30]

      Defined as less than 5% donor chimerism in the cluster of differentiation (CD)3 and CD33 selected cell populations at any time after transplantation. Will be analyzed using KM method.

    4. Cumulative Incidence of Grade III-IV Acute GVHD [Day 100]

      Determined by the standard bone marrow transplant (BMT) Clinical Trials Network criteria (BMTCTN). Will be analyzed using KM method, a Graft versus Host Disease (GVHD) grade III-IV will be obtained from the KM estimates along with 95% confidence intervals.

    5. Cumulative Incidence of Chronic GVHD According to BMTCTN [Up to 1 year]

      Will be summarized with a proportion and a 95% confidence interval.

    6. Number of Participants With Complete Remission After Transplantation [Up to 1 year]

    7. Progression Free Survival [Up to 1 year]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must meet one of two disease criteria:

    • Acute myelogenous leukemia (AML) within one of the following categories:

    • Primary induction failure (PIF): patients who have not achieved a complete remission following initial diagnosis and after at least two induction cycles of chemotherapy consisting of cytarabine and an anthracycline or high-dose cytarabine

    • Relapsed AML: Patients are defined as having relapsed disease if they entered a complete remission confirmed with a bone marrow biopsy following initial treatment, and then were found to have morphological or cytogenetic evidence of recurrent disease on a subsequent bone marrow exam

    • Any complete remission (CR) 2 or greater: CR must be defined using a bone marrow exam taken at least 21 days since the last chemotherapy (including a methyltransferase inhibitor), and may include CRp (morphologic CR without peripheral platelet recovery)

    • CR1 with high-risk features: includes patients with treatment-related AML, secondary AML (following myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN)), high-risk cytogenetic or molecular phenotype (by National Comprehensive Cancer Network (NCCN) criteria)

    • Untreated AML (> 20% blasts on a bone marrow) arising from a previous confirmed diagnosis of MDS or MPN (excluding BCR-ABL (a genetic mutation) positive diseases).

    • Myelodysplastic syndromes within one of the following categories:

    • High-risk myelodysplastic syndrome (MDS) at diagnosis as defined by the International Prognostic Scoring System (IPSS) or World Health Organization (WHO) classification based Prognostic Scoring System (WPSS)

    • Transfusion dependent MDS (either red blood cells (RBC) or platelet dependent) without a hematologic response to at least 4 months of methyltransferase inhibitor (MTI) therapy; hematological response is defined as transfusion independence for two or more months

    • Progressive MDS following at least 4 months of MTI therapy; progression is defined as resumption of transfusion dependence after at least two months of transfusion independence OR increase of marrow blasts by 50% from pretreatment OR overall blasts over 10% of marrow cells at any time after treatment

    • Available related donor that is at least an allele level haplotype-match at human leukocyte antigen (HLA)- A, B, C, DP Beta 1 (DRB1) and DPB1 loci (DPB1 matching according to the "permissive - non-permissive" dichotomy as stated by University of Wisconsin (UW) Histocompatibility Laboratory); a minimum match of 5/10 loci is required; an unrelated donor search is not required for a patient to be eligible for this protocol

    • Karnofsky score of 60% or better (requires occasional assistance, but is able to care for most of his/her needs)

    • Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for hemoglobin > 40%; and forced expiratory volume in one second (FEV1) > 50%

    • Ejection fraction (EF) >= 50% and no uncontrolled angina, symptomatic ventricular arrhythmias, or electrocardiogram (ECG) evidence of active ischemia

    • Serum creatinine within normal range for age, or if serum creatinine outside normal range, then renal function (estimated glomerular filtration rate (GFR) by modification of diet in renal disease (MDRD) formula) > 40 mL/min/1.73 m^2

    • Women of child bearing potential must have a negative pregnancy test within 14 days prior to study registration and agree to use adequate birth control during study treatment

    • Voluntary written consent

    • Patients must be 28 days from the end of the last induction course or at least 14 days from completion of previous methyltransferase inhibitor therapy (azacitidine or decitabine) at the time of registration

    • DONOR: Donors must be at least HLA-haploidentical first degree relatives of the patients; eligible donors include biological parents, siblings, half-siblings or children

    • DONOR: Age >= 18 years and =< 60 years

    • DONOR: Donors must meet the selection criteria prior to the start of the recipient's pre-transplant conditioning regimen as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened according to the American Association of Blood Banks (AABB) guidelines and UW Bone Marrow Transplant (BMT) program standard operating procedure (SOP)

    Exclusion Criteria:
    • Active central nervous system (CNS) leukemia within two weeks of registration; patients with a history of CNS leukemia must have adequate treatment as defined by at least two negative spinal fluid assessments separated by at least one week; patients who have received cranial radiation therapy (XRT) must still be eligible to receive total body irradiation to 4 Gy

    • New or active infection as determined by fever, unexplained pulmonary infiltrate or sinusitis on radiographic assessment; infections diagnosed within 4 weeks of registration must be determined to be controlled or resolving prior to treatment

    • Active human immunodeficiency virus (HIV), hepatitis A, B or C infection

    • Allergy or hypersensitivity to agents used within the treatment protocol

    • DONOR: Recipient derived anti-donor high-titer (> 3000 MFI) HLA antibody as determined by Luminex assay

    • DONOR: Not suitable for donation according to UW BMT program donor selection SOP

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792

    Sponsors and Collaborators

    • University of Wisconsin, Madison
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Mark Juckett, University of Wisconsin, Madison

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    University of Wisconsin, Madison
    ClinicalTrials.gov Identifier:
    NCT01707004
    Other Study ID Numbers:
    • HO11421
    • NCI-2012-01325
    • 2012-0217
    • 2017-0116
    • P30CA014520
    • A534260
    • SMPH/MEDICINE/MEDICINE*H
    First Posted:
    Oct 15, 2012
    Last Update Posted:
    Nov 21, 2019
    Last Verified:
    May 1, 2019

    Study Results

    Participant Flow

    Recruitment Details Recruitment of high risk BMT patients with active disease at time of transplant or very high risk to relapse post-transplant.
    Pre-assignment Detail
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Period Title: Overall Study
    STARTED 20
    COMPLETED 17
    NOT COMPLETED 3

    Baseline Characteristics

    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Overall Participants 20
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    11
    55%
    >=65 years
    9
    45%
    Sex: Female, Male (Count of Participants)
    Female
    6
    30%
    Male
    14
    70%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    20
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    20
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    20
    100%
    Donor Type (Count of Participants)
    Matched Related
    5
    25%
    Haplo-identical
    12
    60%
    Disease Risk by DRI (Count of Participants)
    Low Risk
    0
    0%
    Intermediate Risk
    2
    10%
    High Risk
    13
    65%
    Very High Risk
    5
    25%
    HCT-CI Score (Count of Participants)
    0
    5
    25%
    1-2
    7
    35%
    3+
    8
    40%
    Disease Status (participants) [Number]
    AML
    15
    75%
    Primary Induction Failure
    6
    30%
    Relapsed Disease
    7
    35%
    CR1 with high risk features
    2
    10%
    MDS
    5
    25%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS)
    Description Will be analyzed using Kaplan-Meier (KM) method, and OS will be obtained from the KM estimates along with 95% confidence intervals.
    Time Frame Day 100

    Outcome Measure Data

    Analysis Population Description
    (2 patients did not receive a transplant due to infectious complications, 1 patient received transplant off protocol)
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Number (95% Confidence Interval) [percentage of participants]
    64.7
    323.5%
    2. Secondary Outcome
    Title Time to Neutrophil Recovery
    Description Defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/ul for three consecutive measurements on different days. Will be summarized with mean and standard deviation or median and interquartile range, and the change will be tested using a one-sample paired t-test at a two-tailed significance level of 0.05.
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Mean (95% Confidence Interval) [days]
    16
    3. Secondary Outcome
    Title Percentage of Participants With Platelet Recovery by Day 30
    Description Platelet recovery is defined as the first day of a platelet count greater than 20,000/mm^3 with no platelet transfusions. Will be summarized with mean and standard deviation or median and interquartile range, and the change will be tested using a one-sample paired t-test at a two-tailed significance level of 0.05.
    Time Frame Up to day 30

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Number (95% Confidence Interval) [percentage with plt engraftment, day 30]
    58
    4. Secondary Outcome
    Title Number of Participants With Primary Graft Failure
    Description Defined as less than 5% donor chimerism in the cluster of differentiation (CD)3 and CD33 selected cell populations at any time after transplantation. Will be analyzed using KM method.
    Time Frame Day 30

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Count of Participants [Participants]
    0
    0%
    5. Secondary Outcome
    Title Cumulative Incidence of Grade III-IV Acute GVHD
    Description Determined by the standard bone marrow transplant (BMT) Clinical Trials Network criteria (BMTCTN). Will be analyzed using KM method, a Graft versus Host Disease (GVHD) grade III-IV will be obtained from the KM estimates along with 95% confidence intervals.
    Time Frame Day 100

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Number (95% Confidence Interval) [percentage of participants]
    27.8
    139%
    6. Secondary Outcome
    Title Cumulative Incidence of Chronic GVHD According to BMTCTN
    Description Will be summarized with a proportion and a 95% confidence interval.
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Number (95% Confidence Interval) [percentage]
    40.7
    7. Secondary Outcome
    Title Number of Participants With Complete Remission After Transplantation
    Description
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Count of Participants [Participants]
    14
    70%
    8. Secondary Outcome
    Title Progression Free Survival
    Description
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Decitabine + Bone Marrow Transplant
    Arm/Group Description Pre-transplant Decitabine followed by Bone Marrow Transplant.
    Measure Participants 17
    Median (95% Confidence Interval) [days]
    141

    Adverse Events

    Time Frame Adverse Events (AEs) data were collected from registration to 1 year post-transplant.
    Adverse Event Reporting Description AEs were assessed at regularly scheduled follow up visits where physical exams and labs were performed. AEs reported here include grade 3-5 and adverse events that were not related to the disease state. AEs are reported for all participants who received Decitabine, 17 (+ 1 off protocol) participants who received the transplant.
    Arm/Group Title Decitabine (N=20) Transplant (N=17)
    Arm/Group Description Pre-transplant Decitabine Pre-transplant Decitabine followed by Bone Marrow Transplant
    All Cause Mortality
    Decitabine (N=20) Transplant (N=17)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/20 (75%) 13/17 (76.5%)
    Serious Adverse Events
    Decitabine (N=20) Transplant (N=17)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/20 (0%) 12/17 (70.6%)
    Gastrointestinal disorders
    Abdominal pain 0/20 (0%) 1/17 (5.9%)
    Diarrhea 0/20 (0%) 1/17 (5.9%)
    Immune system disorders
    Immune system disorders - Other, specify 0/20 (0%) 1/17 (5.9%)
    Infections and infestations
    Anorectal infection 0/20 (0%) 1/17 (5.9%)
    Encephalitis infection 0/20 (0%) 1/17 (5.9%)
    Enterocolitis infectious 0/20 (0%) 1/17 (5.9%)
    Infections and infestations - Other, specify 0/20 (0%) 1/17 (5.9%)
    Sepsis 0/20 (0%) 1/17 (5.9%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 0/20 (0%) 1/17 (5.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 0/20 (0%) 1/17 (5.9%)
    Nervous system disorders
    Syncope 0/20 (0%) 1/17 (5.9%)
    Psychiatric disorders
    Delirium 0/20 (0%) 1/17 (5.9%)
    Other (Not Including Serious) Adverse Events
    Decitabine (N=20) Transplant (N=17)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/20 (100%) 17/17 (100%)
    Blood and lymphatic system disorders
    Anemia 20/20 (100%) 65 17/17 (100%) 202
    Febrile Neutropenia 2/20 (10%) 3 6/17 (35.3%) 7
    Cardiac disorders
    Sinus tachycardia 6/20 (30%) 8 11/17 (64.7%) 30
    Atrial fibrillation 0/20 (0%) 0 1/17 (5.9%) 1
    Cardiac disorders - Other, specify 0/20 (0%) 0 1/17 (5.9%) 1
    Palpitations 0/20 (0%) 0 1/17 (5.9%) 2
    Sinus bradycardia 0/20 (0%) 0 1/17 (5.9%) 1
    Ear and labyrinth disorders
    Ear pain 0/20 (0%) 0 1/17 (5.9%) 1
    Hearing impaired 0/20 (0%) 0 1/17 (5.9%) 1
    Eye disorders
    Dry eye 0/20 (0%) 0 4/17 (23.5%) 5
    Eye disorders - Other, specify 0/20 (0%) 0 3/17 (17.6%) 3
    Conjunctivitis 0/20 (0%) 0 2/17 (11.8%) 2
    Cataract 0/20 (0%) 0 1/17 (5.9%) 1
    Photophobia 1/20 (5%) 1 0/17 (0%) 0
    Gastrointestinal disorders
    Nausea 9/20 (45%) 12 15/17 (88.2%) 39
    Mucositis oral 1/20 (5%) 1 17/17 (100%) 49
    Diarrhea 4/20 (20%) 4 15/17 (88.2%) 103
    Vomiting 2/20 (10%) 2 13/17 (76.5%) 43
    Abdominal pain 2/20 (10%) 2 11/17 (64.7%) 22
    Constipation 2/20 (10%) 2 10/17 (58.8%) 16
    Dry mouth 0/20 (0%) 0 10/17 (58.8%) 10
    Dyspepsia 1/20 (5%) 1 5/17 (29.4%) 5
    Hemorrhoids 1/20 (5%) 1 4/17 (23.5%) 6
    Bloating 0/20 (0%) 0 3/17 (17.6%) 3
    Dysphagia 0/20 (0%) 0 3/17 (17.6%) 4
    Esophagitis 0/20 (0%) 0 2/17 (11.8%) 4
    Gastroesophageal reflux disease 0/20 (0%) 0 2/17 (11.8%) 2
    Lower gastrointestinal hemorrhage 0/20 (0%) 0 2/17 (11.8%) 3
    Rectal pain 1/20 (5%) 1 1/17 (5.9%) 1
    Abdominal distension 0/20 (0%) 0 1/17 (5.9%) 2
    Ascites 0/20 (0%) 0 1/17 (5.9%) 1
    Enterocolitis 0/20 (0%) 0 1/17 (5.9%) 2
    Gastrointestinal disorders - Other, specify 0/20 (0%) 0 1/17 (5.9%) 1
    Hemorrhoidal hemorrhage 0/20 (0%) 0 1/17 (5.9%) 1
    Lip pain 0/20 (0%) 0 1/17 (5.9%) 1
    Oral hemorrhage 0/20 (0%) 0 1/17 (5.9%) 1
    Rectal hemorrhage 0/20 (0%) 0 1/17 (5.9%) 1
    General disorders
    Fatigue 11/20 (55%) 13 13/17 (76.5%) 39
    Edema limbs 2/20 (10%) 2 13/17 (76.5%) 28
    Chills 2/20 (10%) 2 7/17 (41.2%) 11
    Fever 2/20 (10%) 2 3/17 (17.6%) 5
    Pain 1/20 (5%) 1 3/17 (17.6%) 3
    Non-cardiac chest pain 0/20 (0%) 0 3/17 (17.6%) 4
    Facial pain 1/20 (5%) 1 1/17 (5.9%) 1
    Edema face 0/20 (0%) 0 1/17 (5.9%) 1
    Infusion related reaction 0/20 (0%) 0 3/17 (17.6%) 3
    Localized edema 0/20 (0%) 0 1/17 (5.9%) 1
    Malaise 0/20 (0%) 0 1/17 (5.9%) 1
    Immune system disorders
    Immune system disorders - Other, specify 0/20 (0%) 0 6/17 (35.3%) 11
    Allergic reaction 0/20 (0%) 0 1/17 (5.9%) 1
    Infections and infestations
    Infections and infestations - Other, specify 4/20 (20%) 4 12/17 (70.6%) 20
    Lung infection 3/20 (15%) 5 4/17 (23.5%) 4
    Urinary tract infection 0/20 (0%) 0 4/17 (23.5%) 6
    Mucosal infection 1/20 (5%) 1 1/17 (5.9%) 1
    Anorectal infection 0/20 (0%) 0 1/17 (5.9%) 1
    Catheter related infection 0/20 (0%) 0 1/17 (5.9%) 1
    Encephalitis infection 0/20 (0%) 0 1/17 (5.9%) 2
    Enterocolitis infectious 0/20 (0%) 0 1/17 (5.9%) 1
    Skin infection 0/20 (0%) 0 1/17 (5.9%) 1
    Upper respiratory infection 0/20 (0%) 0 1/17 (5.9%) 2
    Injury, poisoning and procedural complications
    Bruising 1/20 (5%) 1 2/17 (11.8%) 2
    Fall 1/20 (5%) 1 1/17 (5.9%) 1
    Vascular access complication 0/20 (0%) 0 1/17 (5.9%) 1
    Investigations
    Platelet Count Decreased 18/20 (90%) 57 17/17 (100%) 139
    White Blood Cell Decreased 17/20 (85%) 30 17/17 (100%) 105
    Neutrophil Count Decreased 13/20 (65%) 30 17/17 (100%) 89
    Lymphocyte count decreased 16/20 (80%) 30 16/17 (94.1%) 141
    Aspartate aminotransferase increased 2/20 (10%) 3 15/17 (88.2%) 31
    Alanine aminotransferase increased 2/20 (10%) 2 12/17 (70.6%) 29
    Alkaline phosphatase increased 5/20 (25%) 5 11/17 (64.7%) 22
    Creatinine increased 3/20 (15%) 3 12/17 (70.6%) 26
    Weight loss 2/20 (10%) 4 11/17 (64.7%) 42
    GGT increased 1/20 (5%) 1 12/17 (70.6%) 26
    Blood bilirubin increased 1/20 (5%) 1 10/17 (58.8%) 19
    Weight gain 1/20 (5%) 1 6/17 (35.3%) 12
    INR increased 0/20 (0%) 0 5/17 (29.4%) 6
    Electrocardiogram QT corrected interval prolonged 1/20 (5%) 1 1/17 (5.9%) 1
    Lymphocyte count increased 0/20 (0%) 0 2/17 (11.8%) 3
    CD4 lymphocytes decreased 0/20 (0%) 0 1/17 (5.9%) 1
    Cholesterol high 0/20 (0%) 0 1/17 (5.9%) 2
    Metabolism and nutrition disorders
    Anorexia 4/20 (20%) 4 17/17 (100%) 37
    Hypoalbuminemia 4/20 (20%) 6 17/17 (100%) 80
    Hypokalemia 6/20 (30%) 12 16/17 (94.1%) 76
    Hypomagnesemia 5/20 (25%) 5 17/17 (100%) 135
    Hyponatremia 1/20 (5%) 1 12/17 (70.6%) 28
    Hypernatremia 1/20 (5%) 1 11/17 (64.7%) 37
    Hypophosphatemia 0/20 (0%) 0 12/17 (70.6%) 25
    Hypocalcemia 2/20 (10%) 2 9/17 (52.9%) 22
    Dehydration 2/20 (10%) 2 7/17 (41.2%) 13
    Hyperkalemia 1/20 (5%) 1 7/17 (41.2%) 11
    Hypermagnesemia 0/20 (0%) 0 8/17 (47.1%) 13
    Hyperglycemia 2/20 (10%) 2 6/17 (35.3%) 15
    Hypertriglyceridemia 0/20 (0%) 0 7/17 (41.2%) 9
    Hypercalcemia 0/20 (0%) 0 4/17 (23.5%) 4
    Metabolism and nutrition disorders - Other, specify 0/20 (0%) 0 1/17 (5.9%) 1
    Musculoskeletal and connective tissue disorders
    Generalized muscle weakness 4/20 (20%) 4 7/17 (41.2%) 18
    Back pain 1/20 (5%) 1 5/17 (29.4%) 5
    Bone pain 3/20 (15%) 3 3/17 (17.6%) 5
    Myalgia 1/20 (5%) 1 1/17 (5.9%) 1
    Arthralgia 1/20 (5%) 1 0/17 (0%) 0
    Flank pain 0/20 (0%) 0 1/17 (5.9%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 0/20 (0%) 0 2/17 (11.8%) 3
    Nervous system disorders
    Dysgeusia 1/20 (5%) 1 11/17 (64.7%) 11
    Dizziness 2/20 (10%) 3 8/17 (47.1%) 14
    Headache 3/20 (15%) 4 6/17 (35.3%) 10
    Tremor 0/20 (0%) 0 4/17 (23.5%) 5
    Peripheral sensory neuropathy 1/20 (5%) 1 1/17 (5.9%) 1
    Presyncope 0/20 (0%) 0 2/17 (11.8%) 2
    Syncope 0/20 (0%) 0 1/17 (5.9%) 1
    Psychiatric disorders
    Confusion 0/20 (0%) 0 6/17 (35.3%) 11
    Insomnia 0/20 (0%) 0 4/17 (23.5%) 5
    Anxiety 0/20 (0%) 0 3/17 (17.6%) 3
    Depression 0/20 (0%) 0 2/17 (11.8%) 4
    Delirium 0/20 (0%) 0 1/17 (5.9%) 3
    Renal and urinary disorders
    Hematuria 0/20 (0%) 0 5/17 (29.4%) 10
    Proteinuria 1/20 (5%) 1 3/17 (17.6%) 7
    Renal and urinary disorders - Other, specify 1/20 (5%) 1 3/17 (17.6%) 3
    Acute kidney injury 0/20 (0%) 0 3/17 (17.6%) 6
    Cystitis noninfective 1/20 (5%) 1 2/17 (11.8%) 2
    Urinary frequency 0/20 (0%) 0 3/17 (17.6%) 3
    Urinary tract pain 0/20 (0%) 0 3/17 (17.6%) 3
    Hemoglobinuria 0/20 (0%) 0 2/17 (11.8%) 2
    Urinary incontinence 0/20 (0%) 0 2/17 (11.8%) 3
    Chronic kidney disease 0/20 (0%) 0 1/17 (5.9%) 2
    Urinary urgency 0/20 (0%) 0 1/17 (5.9%) 1
    Urine discoloration 0/20 (0%) 0 1/17 (5.9%) 1
    Reproductive system and breast disorders
    Breast pain 0/20 (0%) 0 1/17 (5.9%) 1
    Genital edema 0/20 (0%) 0 1/17 (5.9%) 1
    Gynecomastia 0/20 (0%) 0 1/17 (5.9%) 1
    Pelvic pain 0/20 (0%) 0 1/17 (5.9%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 0/20 (0%) 0 9/17 (52.9%) 11
    Dyspnea 3/20 (15%) 3 5/17 (29.4%) 9
    Sore throat 1/20 (5%) 1 6/17 (35.3%) 14
    Epistaxis 1/20 (5%) 1 5/17 (29.4%) 10
    Hypoxia 1/20 (5%) 2 4/17 (23.5%) 9
    Pleural effusion 1/20 (5%) 1 3/17 (17.6%) 5
    Hiccups 1/20 (5%) 1 2/17 (11.8%) 2
    Pneumonitis 0/20 (0%) 0 2/17 (11.8%) 5
    Respiratory failure 0/20 (0%) 0 2/17 (11.8%) 2
    Wheezing 0/20 (0%) 0 2/17 (11.8%) 2
    Apnea 0/20 (0%) 0 1/17 (5.9%) 1
    Aspiration 0/20 (0%) 0 1/17 (5.9%) 1
    Laryngeal mucositis 0/20 (0%) 0 1/17 (5.9%) 1
    Nasal congestion 0/20 (0%) 0 1/17 (5.9%) 1
    Pharyngeal mucositis 0/20 (0%) 0 1/17 (5.9%) 1
    Pleuritic pain 1/20 (5%) 1 1/17 (5.9%) 5
    Productive cough 0/20 (0%) 0 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 1/20 (5%) 2 10/17 (58.8%) 19
    Dry skin 2/20 (10%) 2 9/17 (52.9%) 10
    Skin and subcutaneous tissue disorders - Other, specify 2/20 (10%) 2 9/17 (52.9%) 11
    Pruritus 0/20 (0%) 0 4/17 (23.5%) 4
    Pain of skin 0/20 (0%) 0 3/17 (17.6%) 9
    Palmar-plantar erythrodysesthesia syndrome 0/20 (0%) 0 2/17 (11.8%) 2
    Skin ulceration 0/20 (0%) 0 2/17 (11.8%) 2
    Alopecia 0/20 (0%) 0 1/17 (5.9%) 1
    Rash acneiform 0/20 (0%) 0 1/17 (5.9%) 1
    Skin hyperpigmentation 0/20 (0%) 0 1/17 (5.9%) 1
    Vascular disorders
    Hypertension 7/20 (35%) 15 12/17 (70.6%) 88
    Hypotension 4/20 (20%) 4 9/17 (52.9%) 20
    Flushing 0/20 (0%) 0 2/17 (11.8%) 4
    Hematoma 1/20 (5%) 1 2/17 (11.8%) 2
    Thromboembolic event 0/20 (0%) 0 2/17 (11.8%) 2
    Hot flashes 1/20 (5%) 1 1/17 (5.9%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Aric Hall
    Organization UW Carbone Cancer Center
    Phone 608-262-1604
    Email achall@medicine.wisc.edu
    Responsible Party:
    University of Wisconsin, Madison
    ClinicalTrials.gov Identifier:
    NCT01707004
    Other Study ID Numbers:
    • HO11421
    • NCI-2012-01325
    • 2012-0217
    • 2017-0116
    • P30CA014520
    • A534260
    • SMPH/MEDICINE/MEDICINE*H
    First Posted:
    Oct 15, 2012
    Last Update Posted:
    Nov 21, 2019
    Last Verified:
    May 1, 2019