Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults With Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT01092182
Collaborator
(none)
194
30
3
155.2
6.5
0

Study Details

Study Description

Brief Summary

Background:
  • Burkitt lymphoma/leukemia (BL) is highly treatable, but most of the standard therapies require multiple doses of intensive chemotherapy that may require long hospital stays and frequently have severe side effects. In addition, BL is a fairly common type of cancer in patients who also have human immunodeficiency virus (HIV), but treatment outcomes are poor because standard treatments do not work very well in HIV-positive patients and the more intense treatment regimens are highly toxic. New approaches are needed that expand the ways to treat BL with the same efficiency but with reduced side effects.

  • Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) is a standard chemotherapy treatment that consists of the drugs etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. It may be able to treat BL with similar effectiveness but with fewer side effects. Researchers are interested in confirming the results of previous studies that investigated the effectiveness of DA-EPOCH-R in treating BL.

Objectives:
  • To determine the safety and effectiveness of DA-EPOCH-R in treating Burkitt lymphoma.
Eligibility:
  • Individuals at least 18 years of age who have been diagnosed with Burkitt lymphoma and have not had any prior chemotherapy treatments.
Design:
  • Individuals will have a series of blood and other tests to determine their suitability for participating in the study. Eligible participants will be divided into high-risk and low-risk groups based on their disease prognosis and the possibility that the BL may or already has spread into the central nervous system.

  • Participants will receive intravenous infusion of the six chemotherapy drugs in DA-EPOCH-R in 21-day treatment cycles. The exact doses will be adjusted depending on participants white blood cell counts and other tests.

  • High-risk participants will receive six cycles of DA-EPOCH-R. To treat BL that may have entered the central nervous system, high-risk participants will also receive infusions of other chemotherapy drugs into their spinal fluid.

  • Low-risk participants will receive up to six cycles of DA-EPOCH-R, with an additional dose of rituximab during each cycle.

  • Frequent blood and urine tests will be performed during treatment, as well as body imaging scans and other tests of cancer progression as directed by the study doctors. Participants will receive additional medicines to help prevent possible adverse side effects of DA-EPOCH-R.

  • Participants who respond successfully to the treatment will be asked to return for follow-up exams every 3 months for the first 18 months, then every year for the next 3 years. Participants who do not respond successfully to the treatment will be given the opportunity to participate in additional research and treatment protocols, if any are available.

Detailed Description

Background:
  • Burkitt lymphoma/leukemia (BL) is highly curable. Standard treatment employs dose intense multi-agent chemotherapy and though effective is associated with high morbidity. Therefore, novel approaches are needed that improve the therapeutic index of BL while maintaining or improving efficacy. In human immunodeficiency virus (HIV)+ BL, outcome has been poor, mainly due to the use of cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (CHOP) based regimens in this disease.

  • Two National Cancer Institute (NCI) phase II trials have used etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy with 1 or 2 doses of rituximab (R) per cycle in untreated BL. (Dose-adjusted) etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH)-Rituximab has been used in16 HIV negative BL, and 8 HIV positive patients have received 3 to 4 cycles of EPOCHRR to minimize toxicity and risk of opportunistic infections. All patients remain in continuous remission. Treatment was very well tolerated and represents a novel therapeutic strategy in BL.

  • This trial seeks to assess the effectiveness of a risk adaptive approach with DA-EPOCHR in untreated BL (HIV+/-). Because this treatment represents a major conceptual departure from standard treatment, it is important to obtain additional Phase II results in limited/advanced stage BL

  • c-MYC positive Diffuse large B cell (DLBCL) is a rare variant of Diffuse Large B-Cell Lymphoma (DLBCL). There is very little data on the biology of this disease and what the optimal therapeutic approach should be has not been defined. Therefore, based on our impression that this behaves aggressively and is likely characterized by a high tumor proliferation rate, we plan to accrue patients with this disease in addition to BL patients.

  • Plasmablastic lymphoma, another variant of DLBCL is frequently characterized by the activation of MYC and has had a poor outcome historically with standard treatment. We plan to include these patients in the study also. As they are cluster of differentiation 20 (CD20) negative, they will receive DA-EPOCH without Rituximab.

Objectives:
  • Determine progression free survival (PFS), event free survival (EFS) and overall survival (OS) of risk adaptive DA-EPOCH-R in untreated BL and c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma.

  • Assess predictive value of early fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans on PFS.

  • Obtain pilot comparative molecular profiling in HIV negative and positive BL and c- MYC

  • DLBCL, including c-MYC+ plasmablastic lymphoma.
Eligibility:
  • Burkitt lymphoma, c-MYC + DLBCL and c-MYC + plasmablastic lymphoma age greater than or equal to 18 years.

  • No prior treatment except limited-field radiotherapy, short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis.

  • Adequate major organ function unless impairment due to lymphoma.

Study Design:
  • Phase II Study of risk adapted DA-EPOCH-R in BL, c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma

  • Low risk: DA-EPOCH-RR x 3 cycles.

  • High risk , c-MYC + DLBCL and c-MYC+ plasmablastic lymphoma : DA-EPOCH (+/-) R x 6 cycles or 8 cycles in select patients.

  • Cerebrospinal fluid (CSF) cytology and flow cytometry for analysis of BL.

  • High Risk CSF negative - Prophylactic intrathecal treatment

  • CSF positive - Active intrathecal treatment

  • FDG-PET/CT pre- and post-cycle 2 in all patients.

  • A total of 194 patients will be enrolled in the protocol.

Study Design

Study Type:
Interventional
Actual Enrollment :
194 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Dose-Adjusted EPOCH+/-Rituximab in Adults With Untreated Burkitt Lymphoma, c-MYC Positive Diffuse Large B-Cell Lymphoma and Plasmablastic Lymphoma
Actual Study Start Date :
Mar 25, 2010
Actual Primary Completion Date :
Sep 30, 2020
Anticipated Study Completion Date :
Feb 28, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group A - Burkitt lymphoma Low Risk Arm

Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles

Drug: EPOCH-RR
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 3 cycles
Other Names:
  • Etoposide
  • Prednisone
  • Vincristine
  • Cyclophosphamide
  • Doxorubicin
  • Rituximab
  • Experimental: Group B - Burkitt lymphoma High Risk Arm

    Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles

    Drug: EPOCH-R
    Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Other Names:
  • Etoposide
  • Prednisone
  • Vincristine
  • Cyclophosphamide
  • Doxorubicin
  • Rituximab
  • Experimental: Group C - DLBCL high risk arm

    Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles

    Drug: EPOCH-R
    Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Other Names:
  • Etoposide
  • Prednisone
  • Vincristine
  • Cyclophosphamide
  • Doxorubicin
  • Rituximab
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Kaplan-Meier Curve Progression Free Survival (PFS) Constructed With an 95% Confidence Interval [Time of progression or death at 4 years]

      PFS is the time interval from start of treatment to documented evidence of disease progression. Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.

    2. Percentage of Participants With Kaplan-Meier Curve Event Free Survival (EFS) Constructed With an 95% Confidence Interval [At 4 years]

      EFS was determined from the date of enrolment in the study until the date of progression, last documentation of disease at or after the last treatment cycle, death, or last follow-up (whichever occurred first). Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.

    3. Percentage of Participants Kaplan-Meier Curve Overall Survival (OS) Constructed With an 95% Confidence Interval [At 4 years]

      OS was calculated from the enrolment date until date of death or last follow-up using the Kaplan Meier. Kaplan-Meier curves were constructed with an 95% confidence interval.

    Secondary Outcome Measures

    1. Kaplan-Meier Progression Free Survival (PFS) Constructed With an 95% Confidence Interval in Participants Who Underwent Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) and/or Computed Tomography (CT) Scans After Cycle 2 [After 2 cycles of therapy and prior to cycle 3]

      The predictive value of early FDG-PET/CT scans on PFS was assessed after cycle 2. PFS is the time interval from start of treatment to documented evidence of disease progression, assessed by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.

    Other Outcome Measures

    1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [Date treatment consent signed to date off study, approximately 102 months and 25 days for Group A, 125 months and 28 days for Group B and 117 months and 29 days for group C.]

      Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • INCLUSION CRITERIA:
    Patients must have one of the following histologic diagnoses:

    -Patients must have Burkitt Lymphoma. Effective with Amendment J (version date: 06/24/2014), the following histologies were removed as the maximum number allowed for these sub-groups has been reached: B-cell lymphoma: unclassifiable with features intermediate between Diffuse Large B cell lymphoma and Burkitt Lymphoma ; c-MYC + Diffuse large B-cell lymphoma (DLBCL) and c-MYC+ plasmablastic lymphoma.

    If questions arise related to diagnosis, please contact the National Cancer Institute (NCI) Principal Investigator, Dr. Mark Roschewski or the NCI study coordinator, A. Nicole Lucas.

    • Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) in patients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials

    • Pathology confirmed by treating institutions Pathology Department.

    • No prior treatment except patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids, cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture.

    • All disease stages.

    • Human immunodeficiency virus (HIV) negative or positive.

    • HIV positive patients on antiretroviral therapy regimen must be willing to suspend all Highly Active Antiretroviral Therapy (HAART) except in circumstances described in section 6.5.

    • Eastern Cooperative Oncology Group (ECOG) 0-4

    • Ability of patient or durable power of attorney (DPA) for healthcare to give informed consent.

    • Hepatitis B + patients may be enrolled at the discretion of the investigator.

    EXCLUSION CRITERIA:
    • Patients with Primary central nervous system (CNS) Lymphoma.

    • Inadequate renal function, defined as serum creatinine (Cr) > 1.5 or creatinine clearance < 50ml/min/1.73m^2 unless lymphoma related.

    • Inadequate hepatic or hematological function: as follows, unless lymphoma-/disease-related: bilirubin greater than 2 mg/dl (total) except greater than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80% unconjugated, absolute neutrophil count (ANC) less than 1000 and platelets less than 75,000.

    • The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, female subject of child-bearing potential not willing to use an acceptable method of birth control(i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and one year beyond treatment completion will not be eligible to participate in the study.

    • Female subject pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-human chorionic gonadotropin (hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for women without child-bearing potential.

    • The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, male subject unwilling to use an acceptable method for contraception for the duration of the study and one year beyond treatment completion, will not be eligible to participate in the study.

    • History of a prior invasive malignancy in past 5 years.

    • Active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If echo is obtained the left ventricular ejection fraction (LVEF) should exceed 40%.

    • Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety.

    • HIV positive patients with advanced immune suppression and evidence of HIV resistant to all combinations of antiretroviral therapy considered at high risk of non lymphoma related death within 12-months due to other acquired immunodeficiency syndrome (AIDS) complications should not be enrolled on the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UC San Diego Moores Cancer Center La Jolla California United States 92093
    2 UCLA Center for Clinical AIDS Research and Education Los Angeles California United States 90025
    3 Emory University /Winship Cancer Institute Atlanta Georgia United States 30322
    4 University of Illinois Chicago Illinois United States 60607
    5 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    6 University of Kentucky /Markey Cancer Center Lexington Kentucky United States 40536
    7 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892
    8 Massachusetts General Hospital Cancer Centers Boston Massachusetts United States 02114
    9 Dana Farber Cancer Institute Boston Massachusetts United States 02115
    10 Beth Israel Deaconess Medical Center Boston Massachusetts United States
    11 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    12 Fairview - Southdale Hospital Edina Minnesota United States
    13 Unity Hospital Fridley Minnesota United States 55432
    14 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    15 Washington University School of Medicine Saint Louis Missouri United States
    16 University of Nebraska Medical Center Omaha Nebraska United States 68198
    17 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    18 Mount Sinai Hospital New York New York United States 10017
    19 Memorial Sloan Kettering Cancer Center New York New York United States 11570
    20 University of Rochester Rochester New York United States 14627
    21 Vidant Oncology-Kinston Kinston North Carolina United States 28501
    22 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    23 Case Western Reserve University Cleveland Ohio United States 44106-2602
    24 MetroHealth Medical Center Cleveland Ohio United States 44109
    25 Cleveland Clinic Cleveland Ohio United States
    26 University of Tennessee - Knoxville Knoxville Tennessee United States 37996
    27 UT Southwestern /Simmons Cancer Center- Dallas Dallas Texas United States 75390
    28 MD Anderson Cancer Center Houston Texas United States 77030-4096
    29 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    30 Froedtert and the Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Mark J Roschewski, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Mark Roschewski, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01092182
    Other Study ID Numbers:
    • 100052
    • 10-C-0052
    First Posted:
    Mar 24, 2010
    Last Update Posted:
    Nov 3, 2021
    Last Verified:
    Nov 1, 2021
    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
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Mark Roschewski, M.D., Principal Investigator, National Cancer Institute (NCI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Low-risk Burkitt Lymphoma (BL) High-Risk Burkitt Lymphoma (BL) High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles High-Risk Diffuse Large B Cell Lymphoma Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Period Title: Overall Study
    STARTED 15 98 81
    COMPLETED 14 80 53
    NOT COMPLETED 1 18 28

    Baseline Characteristics

    Arm/Group Title Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL) Total
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Total of all reporting groups
    Overall Participants 15 98 81 194
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    13
    86.7%
    84
    85.7%
    55
    67.9%
    152
    78.4%
    >=65 years
    2
    13.3%
    14
    14.3%
    26
    32.1%
    42
    21.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.47
    (14.85)
    46.35
    (17.53)
    57.47
    (14)
    51.39
    (16.74)
    Sex: Female, Male (Count of Participants)
    Female
    4
    26.7%
    20
    20.4%
    20
    24.7%
    44
    22.7%
    Male
    11
    73.3%
    78
    79.6%
    61
    75.3%
    150
    77.3%
    Race/Ethnicity, Customized (Count of Participants)
    Black or African American
    2
    13.3%
    16
    16.3%
    6
    7.4%
    24
    12.4%
    White
    11
    73.3%
    65
    66.3%
    66
    81.5%
    142
    73.2%
    Indian or Alaska Native
    1
    6.7%
    0
    0%
    0
    0%
    1
    0.5%
    Indian or Alaska Native + White
    0
    0%
    1
    1%
    0
    0%
    1
    0.5%
    Asian
    1
    6.7%
    5
    5.1%
    2
    2.5%
    8
    4.1%
    Race Unknown/Not Reported
    0
    0%
    11
    11.2%
    7
    8.6%
    18
    9.3%
    Hispanic or Latino
    1
    6.7%
    10
    10.2%
    4
    4.9%
    15
    7.7%
    Not Hispanic or Latino
    14
    93.3%
    80
    81.6%
    72
    88.9%
    166
    85.6%
    Ethnicity Unknown/Not Reported
    0
    0%
    8
    8.2%
    5
    6.2%
    13
    6.7%
    Region of Enrollment (participants) [Number]
    United States
    15
    100%
    98
    100%
    81
    100%
    194
    100%
    Eastern Cooperative Oncology Group (ECOG) (Count of Participants)
    0
    11
    73.3%
    39
    39.8%
    26
    32.1%
    76
    39.2%
    1
    4
    26.7%
    38
    38.8%
    37
    45.7%
    79
    40.7%
    2
    0
    0%
    14
    14.3%
    9
    11.1%
    23
    11.9%
    3
    0
    0%
    4
    4.1%
    7
    8.6%
    11
    5.7%
    4
    0
    0%
    3
    3.1%
    2
    2.5%
    5
    2.6%
    Baseline Risk Stratification (Count of Participants)
    Low Risk
    15
    100%
    0
    0%
    0
    0%
    15
    7.7%
    High Risk
    0
    0%
    98
    100%
    81
    100%
    179
    92.3%
    International Prognostic Index Score 0-5 (Count of Participants)
    0
    12
    80%
    8
    8.2%
    7
    8.6%
    27
    13.9%
    1
    3
    20%
    19
    19.4%
    7
    8.6%
    29
    14.9%
    2
    0
    0%
    20
    20.4%
    28
    34.6%
    48
    24.7%
    3
    0
    0%
    24
    24.5%
    30
    37%
    54
    27.8%
    4
    0
    0%
    24
    24.5%
    5
    6.2%
    29
    14.9%
    5
    0
    0%
    3
    3.1%
    4
    4.9%
    7
    3.6%
    Histology (Count of Participants)
    High Grade B Cell Lymphoma Double-hit (HGBL DH)
    NA
    NaN
    NA
    NaN
    24
    29.6%
    NA
    NaN
    High Grade B Cell Lymphoma Not Otherwise Specified (HGBL NOS)
    NA
    NaN
    NA
    NaN
    12
    14.8%
    NA
    NaN
    Diffuse Large B-Cell Lymphoma (DLBCL)
    NA
    NaN
    NA
    NaN
    44
    54.3%
    NA
    NaN
    Plasmablastic
    NA
    NaN
    NA
    NaN
    1
    1.2%
    NA
    NaN

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Kaplan-Meier Curve Progression Free Survival (PFS) Constructed With an 95% Confidence Interval
    Description PFS is the time interval from start of treatment to documented evidence of disease progression. Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
    Time Frame Time of progression or death at 4 years

    Outcome Measure Data

    Analysis Population Description
    Those participants that were not analyzed for PFS were screen failures (did not have MYC+ Diffuse Large B-Cell Lymphoma (DLBCL).
    Arm/Group Title Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Measure Participants 15 98 53
    Number (95% Confidence Interval) [percentage of participants]
    100
    666.7%
    82.1
    83.8%
    71.0
    87.7%
    2. Primary Outcome
    Title Percentage of Participants With Kaplan-Meier Curve Event Free Survival (EFS) Constructed With an 95% Confidence Interval
    Description EFS was determined from the date of enrolment in the study until the date of progression, last documentation of disease at or after the last treatment cycle, death, or last follow-up (whichever occurred first). Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
    Time Frame At 4 years

    Outcome Measure Data

    Analysis Population Description
    Those participants that were not analyzed for EFS were screen failures (did not have MYC+ Diffuse Large B-Cell Lymphoma (DLBCL).
    Arm/Group Title Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Measure Participants 15 98 53
    Number (95% Confidence Interval) [percentage of participants]
    100
    666.7%
    82.1
    83.8%
    71.0
    87.7%
    3. Primary Outcome
    Title Percentage of Participants Kaplan-Meier Curve Overall Survival (OS) Constructed With an 95% Confidence Interval
    Description OS was calculated from the enrolment date until date of death or last follow-up using the Kaplan Meier. Kaplan-Meier curves were constructed with an 95% confidence interval.
    Time Frame At 4 years

    Outcome Measure Data

    Analysis Population Description
    Those participants that were not analyzed for OS were screen failures (did not have MYC+ Diffuse Large B-Cell Lymphoma (DLBCL).
    Arm/Group Title Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Measure Participants 15 98 53
    Number (95% Confidence Interval) [percentage of participants]
    100
    666.7%
    84.9
    86.6%
    76.7
    94.7%
    4. Secondary Outcome
    Title Kaplan-Meier Progression Free Survival (PFS) Constructed With an 95% Confidence Interval in Participants Who Underwent Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) and/or Computed Tomography (CT) Scans After Cycle 2
    Description The predictive value of early FDG-PET/CT scans on PFS was assessed after cycle 2. PFS is the time interval from start of treatment to documented evidence of disease progression, assessed by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
    Time Frame After 2 cycles of therapy and prior to cycle 3

    Outcome Measure Data

    Analysis Population Description
    51/98 participants and 34/81 participants did not receive a PET scan.
    Arm/Group Title Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Measure Participants 15 51 34
    Number (95% Confidence Interval) [percentage of participants]
    100
    666.7%
    90.0
    91.8%
    78.7
    97.2%
    5. Other Pre-specified Outcome
    Title Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
    Description Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Date treatment consent signed to date off study, approximately 102 months and 25 days for Group A, 125 months and 28 days for Group B and 117 months and 29 days for group C.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    Measure Participants 15 98 81
    Count of Participants [Participants]
    13
    86.7%
    87
    88.8%
    72
    88.9%

    Adverse Events

    Time Frame Date treatment consent signed to date off study, approximately 102 months and 25 days for Group A, 125 months and 28 days for Group B and 117 months and 29 days for group C.
    Adverse Event Reporting Description
    Arm/Group Title Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Arm/Group Description Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
    All Cause Mortality
    Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 16/98 (16.3%) 3/81 (3.7%)
    Serious Adverse Events
    Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/15 (20%) 58/98 (59.2%) 33/81 (40.7%)
    Blood and lymphatic system disorders
    Anemia 1/15 (6.7%) 2 12/98 (12.2%) 21 4/81 (4.9%) 5
    Febrile neutropenia 0/15 (0%) 0 27/98 (27.6%) 48 11/81 (13.6%) 16
    Cardiac disorders
    Atrial fibrillation 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Cardiac arrest 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Cardiac disorders - Other, hypotension 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Chest pain - cardiac 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Myocardial infarction 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Restrictive cardiomyopathy 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Abdominal pain 0/15 (0%) 0 2/98 (2%) 3 1/81 (1.2%) 1
    Colitis 0/15 (0%) 0 2/98 (2%) 2 1/81 (1.2%) 1
    Diarrhea 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 3
    Gastric perforation 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Gastrointestinal disorders - Other, bleeding 0/15 (0%) 0 2/98 (2%) 2 1/81 (1.2%) 1
    Ileus 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Jejunal perforation 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Lower gastrointestinal hemorrhage 0/15 (0%) 0 2/98 (2%) 2 1/81 (1.2%) 1
    Mucositis oral 0/15 (0%) 0 8/98 (8.2%) 11 0/81 (0%) 0
    Nausea 0/15 (0%) 0 2/98 (2%) 2 2/81 (2.5%) 3
    Oral pain 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Pancreatitis 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Small intestinal obstruction 0/15 (0%) 0 1/98 (1%) 2 0/81 (0%) 0
    Vomiting 0/15 (0%) 0 3/98 (3.1%) 3 2/81 (2.5%) 3
    Gastrointestinal disorders - Other, heme positive stool 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Gastrointestinal disorders - Other, odynohagia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    General disorders
    Death NOS 0/15 (0%) 0 10/98 (10.2%) 10 9/81 (11.1%) 9
    Edema limbs 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Fatigue 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Fever 0/15 (0%) 0 6/98 (6.1%) 7 1/81 (1.2%) 1
    General disorders and administration site conditions - Other, specify 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infusion related reaction 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Multi-organ failure 0/15 (0%) 0 1/98 (1%) 1 2/81 (2.5%) 2
    Pain 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations
    Catheter related infection 1/15 (6.7%) 1 0/98 (0%) 0 0/81 (0%) 0
    Device related infection 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, cellulitis 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Lung infection 0/15 (0%) 0 3/98 (3.1%) 3 1/81 (1.2%) 1
    Phlebitis infective 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Sepsis 0/15 (0%) 0 6/98 (6.1%) 6 4/81 (4.9%) 6
    Sinusitis 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Skin infection 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, clostridium difficile 1/15 (6.7%) 1 0/98 (0%) 0 0/81 (0%) 0
    Infections and infestations - Other, influenza A/H1N1 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, Infected Cholecystostomy tube in setting of neutropenia? 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, neutropenic fever 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, liver infection 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Injury, poisoning and procedural complications
    Vascular access complication 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Aspartate aminotransferase increased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Ejection fraction decreased 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Lymphocyte count decreased 1/15 (6.7%) 1 7/98 (7.1%) 14 3/81 (3.7%) 7
    Neutrophil count decreased 1/15 (6.7%) 1 11/98 (11.2%) 26 5/81 (6.2%) 8
    Platelet count decreased 0/15 (0%) 0 6/98 (6.1%) 12 4/81 (4.9%) 6
    White blood cell decreased 0/15 (0%) 0 15/98 (15.3%) 38 5/81 (6.2%) 7
    Metabolism and nutrition disorders
    Dehydration 0/15 (0%) 0 3/98 (3.1%) 3 2/81 (2.5%) 2
    Hyperglycemia 0/15 (0%) 0 2/98 (2%) 2 2/81 (2.5%) 2
    Hypoalbuminemia 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 3
    Hypocalcemia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hypokalemia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hyponatremia 1/15 (6.7%) 1 3/98 (3.1%) 3 2/81 (2.5%) 2
    Hypophosphatemia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Tumor lysis syndrome 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Musculoskeletal and connective tissue disorders
    Bone pain 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplastic syndrome 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Treatment related secondary malignancy 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Nervous system disorders
    Cerebrospinal fluid leakage 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Dizziness 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Headache 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Intracranial hemorrhage 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Syncope 0/15 (0%) 0 0/98 (0%) 0 4/81 (4.9%) 4
    Vasovagal reaction 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Psychiatric disorders
    Hallucinations 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/15 (0%) 0 1/98 (1%) 1 3/81 (3.7%) 4
    Hematuria 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Proteinuria 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Renal and urinary disorders - Other, acute kidney injury 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Bronchopulmonary hemorrhage 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hypoxia 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Pneumonitis 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Respiratory failure 0/15 (0%) 0 1/98 (1%) 1 3/81 (3.7%) 3
    Respiratory, thoracic and mediastinal disorders - Other, specify 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Skin and subcutaneous tissue disorders
    Toxic epidermal necrolysis 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Vascular disorders
    Hematoma 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Hypertension 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Hypotension 0/15 (0%) 0 4/98 (4.1%) 5 2/81 (2.5%) 2
    Thromboembolic event 0/15 (0%) 0 3/98 (3.1%) 3 1/81 (1.2%) 1
    Other (Not Including Serious) Adverse Events
    Group A - Low-risk Burkitt Lymphoma (BL) Group B - High-Risk Burkitt Lymphoma (BL) Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/15 (86.7%) 88/98 (89.8%) 71/81 (87.7%)
    Blood and lymphatic system disorders
    Anemia 6/15 (40%) 9 62/98 (63.3%) 216 53/81 (65.4%) 181
    Blood and lymphatic system disorders - Other, DVT 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Febrile neutropenia 1/15 (6.7%) 1 29/98 (29.6%) 42 22/81 (27.2%) 35
    Leukocytosis 0/15 (0%) 0 3/98 (3.1%) 3 2/81 (2.5%) 2
    Blood and lymphatic system disorders - Other, leukopenia 0/15 (0%) 0 2/98 (2%) 4 0/81 (0%) 0
    Blood and lymphatic system disorders - Other, low ANC 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Blood and lymphatic system disorders - Other, low platelet count 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Blood and lymphatic system disorders - Other, T bili 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Blood and lymphatic system disorders - Other, thrombosis/embolism 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Cardiac disorders
    Acute coronary syndrome 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Atrial fibrillation 0/15 (0%) 0 5/98 (5.1%) 6 2/81 (2.5%) 2
    Atrial flutter 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Cardiac disorders - Other, 23% decreased EF 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Chest pain - cardiac 1/15 (6.7%) 1 1/98 (1%) 1 0/81 (0%) 0
    Palpitations 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Sinus bradycardia 1/15 (6.7%) 1 2/98 (2%) 2 0/81 (0%) 0
    Sinus tachycardia 0/15 (0%) 0 4/98 (4.1%) 4 4/81 (4.9%) 5
    Supraventricular tachycardia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Ear and labyrinth disorders
    Ear pain 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Tinnitus 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Vertigo 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Eye disorders
    Blurred vision 0/15 (0%) 0 3/98 (3.1%) 3 2/81 (2.5%) 2
    Eyelid function disorder 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Floaters 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Photophobia 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Retinal detachment 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Watering eyes 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Gastrointestinal disorders
    Abdominal distension 0/15 (0%) 0 3/98 (3.1%) 3 0/81 (0%) 0
    Abdominal infection 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Abdominal pain 2/15 (13.3%) 2 8/98 (8.2%) 11 5/81 (6.2%) 5
    Anal fistula 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Ascites 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Bloating 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Colitis 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Constipation 6/15 (40%) 6 20/98 (20.4%) 23 22/81 (27.2%) 37
    Diarrhea 0/15 (0%) 0 18/98 (18.4%) 20 17/81 (21%) 22
    Dry mouth 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Dyspepsia 0/15 (0%) 0 2/98 (2%) 3 3/81 (3.7%) 3
    Dysphagia 0/15 (0%) 0 4/98 (4.1%) 4 2/81 (2.5%) 2
    Enterocolitis 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Esophageal hemorrhage 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Esophagitis 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Fecal incontinence 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Flatulence 1/15 (6.7%) 1 0/98 (0%) 0 2/81 (2.5%) 2
    Gastritis 1/15 (6.7%) 1 1/98 (1%) 1 2/81 (2.5%) 2
    Gastroesophageal reflux disease 0/15 (0%) 0 2/98 (2%) 2 2/81 (2.5%) 2
    Gastrointestinal disorders - Other, epigastric pain 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hemorrhoids 0/15 (0%) 0 3/98 (3.1%) 3 1/81 (1.2%) 2
    Ileus 0/15 (0%) 0 1/98 (1%) 1 3/81 (3.7%) 4
    Mucositis oral 1/15 (6.7%) 1 23/98 (23.5%) 47 20/81 (24.7%) 31
    Nausea 1/15 (6.7%) 3 18/98 (18.4%) 25 11/81 (13.6%) 16
    Oral hemorrhage 1/15 (6.7%) 1 0/98 (0%) 0 0/81 (0%) 0
    Oral pain 1/15 (6.7%) 1 1/98 (1%) 1 1/81 (1.2%) 5
    Rectal hemorrhage 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Stomach pain 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Toothache 1/15 (6.7%) 1 2/98 (2%) 2 0/81 (0%) 0
    Typhlitis 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Vomiting 0/15 (0%) 0 9/98 (9.2%) 14 7/81 (8.6%) 8
    General disorders
    Chills 1/15 (6.7%) 1 5/98 (5.1%) 6 2/81 (2.5%) 2
    Death NOS 0/15 (0%) 0 2/98 (2%) 2 1/81 (1.2%) 1
    Edema limbs 0/15 (0%) 0 3/98 (3.1%) 3 11/81 (13.6%) 12
    Fatigue 4/15 (26.7%) 7 22/98 (22.4%) 28 22/81 (27.2%) 35
    Fever 1/15 (6.7%) 1 13/98 (13.3%) 16 8/81 (9.9%) 10
    Flu like symptoms 0/15 (0%) 0 1/98 (1%) 1 2/81 (2.5%) 2
    Gait disturbance 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    General disorders and administration site conditions - Other, cerebellar infarct 0/15 (0%) 0 2/98 (2%) 3 0/81 (0%) 0
    Infusion related reaction 0/15 (0%) 0 2/98 (2%) 2 3/81 (3.7%) 3
    Neck edema 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Pain 1/15 (6.7%) 1 10/98 (10.2%) 14 6/81 (7.4%) 7
    General disorders and administration site conditions - Other, sacral pressure ulcer 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    General disorders and administration site conditions - Other, thalmic infarct 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hepatobiliary disorders
    Hepatic failure 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Immune system disorders
    Allergic reaction 0/15 (0%) 0 3/98 (3.1%) 3 2/81 (2.5%) 2
    Infections and infestations
    Anorectal infection 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Bladder infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Bronchial infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Catheter related infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Enterocolitis infectious 0/15 (0%) 0 2/98 (2%) 2 4/81 (4.9%) 4
    Esophageal infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Eye infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Infections and infestations - Other, bacteremia 1/15 (6.7%) 1 0/98 (0%) 0 0/81 (0%) 0
    Lung infection 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Mucosal infection 0/15 (0%) 0 8/98 (8.2%) 12 4/81 (4.9%) 5
    Peritoneal infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Rhinitis infective 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Sepsis 0/15 (0%) 0 1/98 (1%) 1 2/81 (2.5%) 2
    Sinusitis 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Skin infection 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Upper respiratory infection 1/15 (6.7%) 1 0/98 (0%) 0 1/81 (1.2%) 1
    Urethral infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Urinary tract infection 0/15 (0%) 0 8/98 (8.2%) 9 8/81 (9.9%) 11
    Wound infection 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Infections and infestations - Other, Blood 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, blood infection 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, blood, E. coli 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, bacteremia, Klebsiella infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Infections and infestations - Other, candida oral infection 0/15 (0%) 0 1/98 (1%) 2 0/81 (0%) 0
    Infections and infestations - Other, clostridium difficile 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, CMV reactivation 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Infections and infestations - Other, encephalitis, persistent 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, gastrointestinal tract 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, infection 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Infections and infestations - Other, infection-oral 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, L posterior lung 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, left orbital cellulitis 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, MRSA 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, oral cavity 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, parasitic infection 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, PICC line infection 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, polymicrobial bacteremia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, throat 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Infections and infestations - Other, thrush 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, VRE 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Infections and infestations - Other, VRE-blood stream 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, blood, candida glabrata 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Infections and infestations - Other, herpes simplex oral ulcer 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Infections and infestations - Other, oral thrush 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Injury, poisoning and procedural complications
    Bruising 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Fall 0/15 (0%) 0 2/98 (2%) 2 1/81 (1.2%) 1
    Investigations
    Activated partial thromboplastin time prolonged 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Alanine aminotransferase increased 2/15 (13.3%) 2 15/98 (15.3%) 23 7/81 (8.6%) 14
    Alkaline phosphatase increased 0/15 (0%) 0 7/98 (7.1%) 10 12/81 (14.8%) 21
    Aspartate aminotransferase increased 1/15 (6.7%) 1 13/98 (13.3%) 18 7/81 (8.6%) 12
    Blood bilirubin increased 2/15 (13.3%) 2 9/98 (9.2%) 13 5/81 (6.2%) 9
    CD4 lymphocytes decreased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Cardiac troponin I increased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Cardiac troponin T increased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Creatinine increased 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Elevated LFT's 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Elevated bilirubin 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    GGT increased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Investigations - Other, disease progression 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Lipase increased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Lymphocyte count decreased 5/15 (33.3%) 11 54/98 (55.1%) 277 49/81 (60.5%) 239
    Lymphocyte count increased 0/15 (0%) 0 1/98 (1%) 1 3/81 (3.7%) 3
    Neutrophil count decreased 5/15 (33.3%) 6 55/98 (56.1%) 201 49/81 (60.5%) 178
    Pancreatic enzymes decreased 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Platelet count decreased 3/15 (20%) 3 52/98 (53.1%) 161 43/81 (53.1%) 159
    Urine output decreased 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Weight gain 0/15 (0%) 0 3/98 (3.1%) 5 1/81 (1.2%) 1
    Weight loss 0/15 (0%) 0 2/98 (2%) 2 5/81 (6.2%) 8
    White blood cell decreased 7/15 (46.7%) 10 47/98 (48%) 212 52/81 (64.2%) 218
    Investigations - Other, heartburn 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Investigations - Other, night sweats 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Investigations - Other, fluid overload 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Metabolism and nutrition disorders
    Alkalosis 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Anorexia 1/15 (6.7%) 1 9/98 (9.2%) 10 6/81 (7.4%) 7
    Dehydration 0/15 (0%) 0 7/98 (7.1%) 11 2/81 (2.5%) 3
    Glucose intolerance 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hypercalcemia 0/15 (0%) 0 1/98 (1%) 1 3/81 (3.7%) 3
    Hyperglycemia 0/15 (0%) 0 16/98 (16.3%) 42 15/81 (18.5%) 37
    Hyperkalemia 0/15 (0%) 0 3/98 (3.1%) 3 3/81 (3.7%) 3
    Hypermagnesemia 1/15 (6.7%) 1 2/98 (2%) 2 3/81 (3.7%) 4
    Hypernatremia 0/15 (0%) 0 4/98 (4.1%) 5 8/81 (9.9%) 17
    Hypertriglyceridemia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hyperuricemia 0/15 (0%) 0 1/98 (1%) 1 2/81 (2.5%) 2
    Hypoalbuminemia 0/15 (0%) 0 18/98 (18.4%) 32 15/81 (18.5%) 27
    Hypocalcemia 0/15 (0%) 0 17/98 (17.3%) 32 17/81 (21%) 28
    Hypoglycemia 0/15 (0%) 0 4/98 (4.1%) 7 3/81 (3.7%) 3
    Hypokalemia 1/15 (6.7%) 1 21/98 (21.4%) 32 18/81 (22.2%) 36
    Hypomagnesemia 0/15 (0%) 0 7/98 (7.1%) 13 6/81 (7.4%) 16
    Hyponatremia 1/15 (6.7%) 1 14/98 (14.3%) 19 6/81 (7.4%) 8
    Hypophosphatemia 2/15 (13.3%) 2 22/98 (22.4%) 36 20/81 (24.7%) 29
    Metabolism and nutrition disorders - Other, elevated LDH 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Tumor lysis syndrome 0/15 (0%) 0 4/98 (4.1%) 4 0/81 (0%) 0
    Metabolism and nutrition disorders - Other, malnutrition 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Back pain 1/15 (6.7%) 1 7/98 (7.1%) 10 7/81 (8.6%) 7
    Bone pain 2/15 (13.3%) 3 9/98 (9.2%) 13 7/81 (8.6%) 10
    Chest wall pain 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Flank pain 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Generalized muscle weakness 1/15 (6.7%) 1 4/98 (4.1%) 7 5/81 (6.2%) 6
    Joint effusion 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Muscle weakness lower limb 0/15 (0%) 0 1/98 (1%) 2 0/81 (0%) 0
    Muscle weakness trunk 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Musculoskeletal and connective tissue disorder - Other, specify 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Myalgia 1/15 (6.7%) 1 0/98 (0%) 0 1/81 (1.2%) 2
    Neck pain 1/15 (6.7%) 1 3/98 (3.1%) 3 1/81 (1.2%) 1
    Non-cardiac chest pain 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Pain in extremity 0/15 (0%) 0 2/98 (2%) 3 3/81 (3.7%) 4
    Musculoskeletal and connective tissue disorder - Other, shin pain with numbness 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Nervous system disorders
    Cerebrospinal fluid leakage 0/15 (0%) 0 2/98 (2%) 3 0/81 (0%) 0
    Cognitive disturbance 0/15 (0%) 0 1/98 (1%) 2 0/81 (0%) 0
    Depressed level of consciousness 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Dizziness 0/15 (0%) 0 7/98 (7.1%) 9 3/81 (3.7%) 5
    Dysgeusia 0/15 (0%) 0 1/98 (1%) 1 5/81 (6.2%) 6
    Dysphasia 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Facial nerve disorder 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Headache 1/15 (6.7%) 2 25/98 (25.5%) 31 11/81 (13.6%) 13
    Memory impairment 0/15 (0%) 0 2/98 (2%) 5 1/81 (1.2%) 1
    Movements involuntary 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Nervous system disorders - Other, numbness in left arm 1/15 (6.7%) 3 0/98 (0%) 0 2/81 (2.5%) 6
    Paresthesia 0/15 (0%) 0 5/98 (5.1%) 5 3/81 (3.7%) 10
    Peripheral motor neuropathy 0/15 (0%) 0 8/98 (8.2%) 9 8/81 (9.9%) 9
    Peripheral sensory neuropathy 5/15 (33.3%) 5 26/98 (26.5%) 33 22/81 (27.2%) 25
    Presyncope 0/15 (0%) 0 2/98 (2%) 4 2/81 (2.5%) 2
    Seizure 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Somnolence 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Syncope 0/15 (0%) 0 5/98 (5.1%) 7 2/81 (2.5%) 2
    Tremor 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Nervous system disorders - Other, neuropathy 1/15 (6.7%) 1 0/98 (0%) 0 1/81 (1.2%) 5
    Nervous system disorders - Other, neuropathy, upper bilateral extremities 2/15 (13.3%) 2 0/98 (0%) 0 0/81 (0%) 0
    Psychiatric disorders
    Agitation 0/15 (0%) 0 2/98 (2%) 2 1/81 (1.2%) 1
    Anxiety 0/15 (0%) 0 1/98 (1%) 1 2/81 (2.5%) 2
    Confusion 0/15 (0%) 0 3/98 (3.1%) 3 2/81 (2.5%) 2
    Delirium 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Delusions 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Depression 0/15 (0%) 0 3/98 (3.1%) 3 1/81 (1.2%) 1
    Insomnia 1/15 (6.7%) 1 10/98 (10.2%) 12 6/81 (7.4%) 6
    Personality change 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Psychiatric disorders - Other, non verbal 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Hematuria 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Renal and urinary disorders - Other, dysuria 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Urinary frequency 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Urinary tract pain 1/15 (6.7%) 1 1/98 (1%) 1 2/81 (2.5%) 2
    Urinary urgency 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Reproductive system and breast disorders
    Scrotal pain 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/15 (0%) 0 1/98 (1%) 1 2/81 (2.5%) 2
    Aspiration 0/15 (0%) 0 0/98 (0%) 0 3/81 (3.7%) 3
    Cough 0/15 (0%) 0 6/98 (6.1%) 6 1/81 (1.2%) 1
    Dyspnea 1/15 (6.7%) 1 8/98 (8.2%) 9 7/81 (8.6%) 9
    Epistaxis 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hiccups 0/15 (0%) 0 3/98 (3.1%) 3 0/81 (0%) 0
    Hoarseness 0/15 (0%) 0 2/98 (2%) 2 1/81 (1.2%) 1
    Hypoxia 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Laryngeal inflammation 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Laryngeal mucositis 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Nasal congestion 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Pharyngeal mucositis 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Pharyngolaryngeal pain 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Pleural effusion 0/15 (0%) 0 1/98 (1%) 1 2/81 (2.5%) 2
    Pneumonitis 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Postnasal drip 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Productive cough 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Pulmonary edema 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Respiratory failure 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Sleep apnea 1/15 (6.7%) 3 1/98 (1%) 1 0/81 (0%) 0
    Sore throat 0/15 (0%) 0 4/98 (4.1%) 5 1/81 (1.2%) 1
    Tracheal fistula 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Skin and subcutaneous tissue disorders
    Alopecia 4/15 (26.7%) 6 9/98 (9.2%) 14 6/81 (7.4%) 6
    Dry skin 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hyperhidrosis 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Nail discoloration 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Nail loss 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Pain of skin 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Papulopustular rash 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Pruritus 0/15 (0%) 0 3/98 (3.1%) 3 1/81 (1.2%) 1
    Rash acneiform 0/15 (0%) 0 0/98 (0%) 0 3/81 (3.7%) 3
    Rash maculo-papular 0/15 (0%) 0 1/98 (1%) 1 1/81 (1.2%) 1
    Rash pustular 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Skin and subcutaneous tissue disorders - Other, abdominal abscess 2/15 (13.3%) 2 4/98 (4.1%) 5 1/81 (1.2%) 1
    Skin hyperpigmentation 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Skin ulceration 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Urticaria 0/15 (0%) 0 0/98 (0%) 0 2/81 (2.5%) 2
    Skin and subcutaneous tissue disorders - Other, blister ball of R foot 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Skin and subcutaneous tissue disorders - Other, dermatitis 0/15 (0%) 0 0/98 (0%) 0 1/81 (1.2%) 1
    Skin and subcutaneous tissue disorders - Other, forehead itching 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Skin and subcutaneous tissue disorders - Other, skin darkening 1/15 (6.7%) 1 0/98 (0%) 0 0/81 (0%) 0
    Skin and subcutaneous tissue disorders - Other, vitiligo 1/15 (6.7%) 1 0/98 (0%) 0 0/81 (0%) 0
    Skin and subcutaneous tissue disorders - Other, pressure ulcer 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Skin and subcutaneous tissue disorders - Other, scalp wound 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Vascular disorders
    Hematoma 0/15 (0%) 0 3/98 (3.1%) 4 0/81 (0%) 0
    Hot flashes 0/15 (0%) 0 1/98 (1%) 1 0/81 (0%) 0
    Hypertension 1/15 (6.7%) 1 5/98 (5.1%) 9 6/81 (7.4%) 12
    Hypotension 0/15 (0%) 0 8/98 (8.2%) 9 6/81 (7.4%) 8
    Superficial thrombophlebitis 0/15 (0%) 0 2/98 (2%) 2 0/81 (0%) 0
    Thromboembolic event 0/15 (0%) 0 6/98 (6.1%) 6 5/81 (6.2%) 5

    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 Dr. Mark J. Roschewski
    Organization National Cancer Institute
    Phone 240-760-6183
    Email roschewskimj@nih.gov
    Responsible Party:
    Mark Roschewski, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01092182
    Other Study ID Numbers:
    • 100052
    • 10-C-0052
    First Posted:
    Mar 24, 2010
    Last Update Posted:
    Nov 3, 2021
    Last Verified:
    Nov 1, 2021