A Phase 2, Multicenter, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01466153
Collaborator
(none)
183
Enrollment
54
Locations
3
Arms
47
Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall purpose of the study was to determine if MEDI-551, when used in combination with salvage chemotherapy (bendamustine) in participants with relapsed or refractory CLL who are not eligible for Autologous Stem Cell Transplant (ASCT), had superior efficacy compared to rituximab in the same population.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
183 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Open-label Study of MEDI-551 and Bendamustine vs Rituximab and Bendamustine in Adults With Relapsed or Refractory CLL
Study Start Date :
Feb 7, 2012
Actual Primary Completion Date :
Jan 8, 2016
Actual Study Completion Date :
Jan 8, 2016

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Rituximab + Bendamustine

Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.

Drug: Rituximab
Rituximab was administered by IV infusion as a dose of 375 mg/m^2 on Day 2 of Cycle 1 and then at 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycles
Other Names:
  • Rituxan; MabThera
  • Drug: Bendamustine
    Bendamustine was administered by IV infusion as a dose of 70 mg/m^2 on Day 1 and Day 2 of each 5 subsequent 28-day cycle.

    Experimental: MEDI-551 2 mg/kg + Bendamustine

    MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

    Drug: Bendamustine
    Bendamustine was administered by IV infusion as a dose of 70 mg/m^2 on Day 1 and Day 2 of each 5 subsequent 28-day cycle.

    Drug: MEDI-551
    MEDI-551 was administered at 2 mg/kg or 4 mg/kg by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycles.

    Experimental: MEDI-551 4 mg/kg + Bendamustine

    MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

    Drug: Bendamustine
    Bendamustine was administered by IV infusion as a dose of 70 mg/m^2 on Day 1 and Day 2 of each 5 subsequent 28-day cycle.

    Drug: MEDI-551
    MEDI-551 was administered at 2 mg/kg or 4 mg/kg by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycles.

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      ORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.

    Secondary Outcome Measures

    1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) [From time of consent to 90 days post last dose]

      An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug (MEDI-551). A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 90 that were absent before treatment or that worsened relative to pre-treatment state. An AESIs was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through Day 90 after the last dose of study drug.Hepatic function abnormality and infusion reactions resulting in discontinuation were considered as AESIs.

    2. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as AEs [From time of consent to 90 days post last dose]

      An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.

    3. Number of Participants With Abnormal Vital Signs and Electrocardiogram Reported as AEs [From time of consent to 90 days post last dose]

      AEs observed in participants with clinically significant ECG abnormalities were assessed.

    4. Complete Response Rate [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      Complete response was as per IWG was the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

    5. Minimal Residual Disease Negative Complete Response (CR) Rate [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      The MRD-negative CR rate was defined as the percentage of participants who achieved CR and became MRD-negative as determined by flow cytometry. CR as per International Working Group (IWG) was complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

    6. Time to Response [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      Time to response was evaluated using the Kaplan-Meier method.

    7. Time to Disease Progression (TTP) [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      TTP was defined as the time from onset of treatment with study drug until first evidence/diagnosis of progressive disease or - in the absence of any diagnosis of progressive disease - until the participant´s death.

    8. Progression Free Survival (PFS) [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      PFS was measured from the start of treatment with study drug until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.

    9. Overall Survival (OS) [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      OS was determined as the time from the start of treatment with study drug until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.

    10. Number of Participants Who Developed Detectable Anti-drug Antibodies (ADA) [From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)]

      A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.

    11. Terminal Half Life (t1/2) of MEDI-551 [Pre-infusion and 1 hour post infusion on Days 2 and 8, Days 15 and 22 of cycle 1]

      Terminal phase elimination half-life (T1/2) was the time required for half of the drug to be eliminated from the serum.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically confirmed B-cell Chronic Lymphocytic Leukemia (CLL) according to the National Cancer Institute criteria; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; Adequate hematological function
    Exclusion Criteria:
    • Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational, or hormonal therapy for treatment of lymphoma within 28 days prior to treatment;

    • Exposure to bendamustine within the 180 days before study enrollment

    • Prior autologous or allogeneic stem cell transplantation (SCT);

    • Clinically significant abnormality on electrocardiogram (ECG) as determined by the treating physician or medical monitor;

    • History of other invasive malignancy within 5 years except for localized/in situ carcinomas;

    • Evidence of active infection, Confirmed current central nervous system involvement by leukemia or lymphoma;

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Research SiteBirminghamAlabamaUnited States
    2Research SiteBurbankCaliforniaUnited States
    3Research SiteLa JollaCaliforniaUnited States
    4Research SitePalm SpringsCaliforniaUnited States
    5Research SiteSkokieIllinoisUnited States
    6Research SiteShreveportLouisianaUnited States
    7Research SiteBaltimoreMarylandUnited States
    8Research SiteDetroitMichiganUnited States
    9Research SiteFargoNorth DakotaUnited States
    10Research SiteDaytonOhioUnited States
    11Research SiteNewarkOhioUnited States
    12Research SiteWatertownSouth DakotaUnited States
    13Research SiteLubbockTexasUnited States
    14Research SiteMorgantownWest VirginiaUnited States
    15Research SiteAntwerpenBelgium
    16Research SiteArlonBelgium
    17Research SiteKortrijkBelgium
    18Research SiteMonsBelgium
    19Research SiteWilrijkBelgium
    20Research SiteYvoirBelgium
    21Research SiteTorontoOntarioCanada
    22Research SiteGreenfield ParkQuebecCanada
    23Research SiteMontrealQuebecCanada
    24Research SiteAmiensFrance
    25Research SiteBayonneFrance
    26Research SiteBordeauxFrance
    27Research SiteLe MansFrance
    28Research SiteLibourne CedexFrance
    29Research SiteMarseilleFrance
    30Research SiteNimesFrance
    31Research SiteDortmundGermany
    32Research SiteEssenGermany
    33Research SiteFreiburgGermany
    34Research SiteMuenchenGermany
    35Research SiteWuerzburgGermany
    36Research SiteHaifaIsrael
    37Research SiteRamat GanIsrael
    38Research SiteBariItaly
    39Research SiteLecceItaly
    40Research SiteMeldolaItaly
    41Research SiteMilanoItaly
    42Research SiteModenaItaly
    43Research SiteNapoliItaly
    44Research SiteOrbassanoItaly
    45Research SitePalermoItaly
    46Research SitePisaItaly
    47Research SiteRavennaItaly
    48Research SiteRiminiItaly
    49Research SiteRomaItaly
    50Research SiteSan Giovanni RotondoItaly
    51Research SiteTorinoItaly
    52Research SiteUdineItaly
    53Research SiteGdyniaPoland
    54Research SiteWarszawaPoland

    Sponsors and Collaborators

    • MedImmune LLC

    Investigators

    • Study Director: MedImmune, MedImmune LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT01466153
    Other Study ID Numbers:
    • CD-ON-MEDI-551-1019
    First Posted:
    Nov 6, 2011
    Last Update Posted:
    May 31, 2017
    Last Verified:
    Apr 1, 2017

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailA total of 182 participants were screened and 159 participants were randomized.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Period Title: Overall Study
    STARTED623661
    COMPLETED331236
    NOT COMPLETED292425

    Baseline Characteristics

    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + BendamustineTOTAL
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.Total of all reporting groups
    Overall Participants623661159
    Age (YEARS) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [YEARS]
    63.4
    (8.8)
    65.1
    (8.7)
    66.3
    (8.9)
    65.1
    (8.8)
    Sex: Female, Male (Count of Participants)
    Female
    16
    25.8%
    14
    38.9%
    18
    29.5%
    48
    30.2%
    Male
    46
    74.2%
    22
    61.1%
    43
    70.5%
    111
    69.8%

    Outcome Measures

    1. Primary Outcome
    TitleObjective Response Rate
    DescriptionORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population includes all participants who were randomized into the study.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants623661
    Number (95% Confidence Interval) [Percentage of Participants]
    59.7
    96.3%
    52.8
    146.7%
    63.9
    104.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rituximab + Bendamustine, MEDI-551 4 mg/kg + Bendamustine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.4475
    Comments
    MethodCochran-Mantel-Haenszel
    Comments
    2. Secondary Outcome
    TitleNumber of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)
    DescriptionAn adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug (MEDI-551). A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 90 that were absent before treatment or that worsened relative to pre-treatment state. An AESIs was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through Day 90 after the last dose of study drug.Hepatic function abnormality and infusion reactions resulting in discontinuation were considered as AESIs.
    Time FrameFrom time of consent to 90 days post last dose

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any investigational product.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants603357
    TEAEs
    58
    93.5%
    33
    91.7%
    57
    93.4%
    TESAEs
    19
    30.6%
    16
    44.4%
    19
    31.1%
    AESIs
    2
    3.2%
    4
    11.1%
    6
    9.8%
    3. Secondary Outcome
    TitleNumber of Participants With Abnormal Clinical Laboratory Parameters Reported as AEs
    DescriptionAn abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
    Time FrameFrom time of consent to 90 days post last dose

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any investigational product.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants603357
    Hyperbilirubinaemia
    0
    0%
    2
    5.6%
    1
    1.6%
    Hypercalcaemia
    1
    1.6%
    0
    0%
    0
    0%
    Hypercholesterolaemia
    1
    1.6%
    0
    0%
    1
    1.6%
    Hyperglycaemia
    4
    6.5%
    2
    5.6%
    1
    1.6%
    Hyperkalaemia
    2
    3.2%
    1
    2.8%
    2
    3.3%
    Hyperlipidaemia
    0
    0%
    1
    2.8%
    0
    0%
    Hypermagnesaemia
    1
    1.6%
    0
    0%
    0
    0%
    Hyperphosphataemia
    0
    0%
    1
    2.8%
    1
    1.6%
    Hypertriglyceridaemia
    1
    1.6%
    0
    0%
    0
    0%
    Hyperuricaemia
    3
    4.8%
    5
    13.9%
    2
    3.3%
    Hypoalbuminaemia
    2
    3.2%
    0
    0%
    2
    3.3%
    Hypocalcaemia
    3
    4.8%
    1
    2.8%
    1
    1.6%
    Hypokalaemia
    6
    9.7%
    1
    2.8%
    4
    6.6%
    Hypomagnesaemia
    2
    3.2%
    2
    5.6%
    1
    1.6%
    Hyponatraemia
    2
    3.2%
    1
    2.8%
    0
    0%
    Alanine Aminotransferase Increased
    1
    1.6%
    0
    0%
    3
    4.9%
    Aspartate Aminotransferase Increased
    1
    1.6%
    0
    0%
    3
    4.9%
    Blood Alkaline Phosphatase Increased
    1
    1.6%
    1
    2.8%
    2
    3.3%
    Blood Bilirubin Increased
    0
    0%
    1
    2.8%
    1
    1.6%
    Blood Cholesterol Decreased
    0
    0%
    0
    0%
    1
    1.6%
    Blood Creatinine Decreased
    1
    1.6%
    0
    0%
    0
    0%
    Blood Creatinine Increased
    1
    1.6%
    2
    5.6%
    1
    1.6%
    Blood Immunoglobulin G Decreased
    0
    0%
    0
    0%
    1
    1.6%
    Blood Lactate Dehydrogenase Increased
    4
    6.5%
    0
    0%
    0
    0%
    Blood Urea Increased
    1
    1.6%
    1
    2.8%
    0
    0%
    Gamma-Glutamyltransferase Increased
    1
    1.6%
    1
    2.8%
    2
    3.3%
    Hepatic enzyme Increased
    1
    1.6%
    0
    0%
    0
    0%
    Anaemia
    18
    29%
    7
    19.4%
    9
    14.8%
    Eosinophilia
    0
    0%
    0
    0%
    1
    1.6%
    Lymphopenia
    4
    6.5%
    3
    8.3%
    1
    1.6%
    Neutropenia
    28
    45.2%
    10
    27.8%
    19
    31.1%
    Thromobocytopenia
    12
    19.4%
    6
    16.7%
    10
    16.4%
    Activated Partial Thromboplastin Time Prolonged
    2
    3.2%
    0
    0%
    0
    0%
    Blood Fibrinogen Increased
    1
    1.6%
    0
    0%
    0
    0%
    Blood Immunoglobulin g Decreased
    0
    0%
    0
    0%
    1
    1.6%
    Haemoglobin Decreased
    0
    0%
    1
    2.8%
    0
    0%
    Lymphocyte Count Decreased
    3
    4.8%
    0
    0%
    2
    3.3%
    Neutrophil Count Decreased
    9
    14.5%
    1
    2.8%
    3
    4.9%
    Platelet Count Decreased
    2
    3.2%
    2
    5.6%
    3
    4.9%
    Prothrombin Time Shortened
    1
    1.6%
    0
    0%
    0
    0%
    Haematuria
    0
    0%
    2
    5.6%
    1
    1.6%
    Proteinuria
    0
    0%
    1
    2.8%
    0
    0%
    White Blood Cells in Urine
    0
    0%
    0
    0%
    1
    1.6%
    4. Secondary Outcome
    TitleNumber of Participants With Abnormal Vital Signs and Electrocardiogram Reported as AEs
    DescriptionAEs observed in participants with clinically significant ECG abnormalities were assessed.
    Time FrameFrom time of consent to 90 days post last dose

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any investigational product.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants603357
    Atrial Fibrillation
    1
    1.6%
    2
    5.6%
    1
    1.6%
    Atrioventricular Block
    1
    1.6%
    0
    0%
    0
    0%
    Palpitations
    0
    0%
    0
    0%
    2
    3.3%
    Sinus Bradycardia
    1
    1.6%
    0
    0%
    0
    0%
    Sinus Tachycardia
    1
    1.6%
    0
    0%
    0
    0%
    Tachycardia
    2
    3.2%
    1
    2.8%
    1
    1.6%
    Pyrexia
    20
    32.3%
    11
    30.6%
    14
    23%
    Dyspnoea
    9
    14.5%
    2
    5.6%
    4
    6.6%
    Dyspnoea Exertional
    3
    4.8%
    1
    2.8%
    0
    0%
    Hypertension
    1
    1.6%
    0
    0%
    1
    1.6%
    Hypotension
    5
    8.1%
    2
    5.6%
    6
    9.8%
    Orthostatic Hypotension
    0
    0%
    0
    0%
    1
    1.6%
    5. Secondary Outcome
    TitleComplete Response Rate
    DescriptionComplete response was as per IWG was the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population includes all participants who were randomized into the study.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants623661
    Number (95% Confidence Interval) [Percentage of Participants]
    6.5
    10.5%
    5.6
    15.6%
    11.5
    18.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rituximab + Bendamustine, MEDI-551 4 mg/kg + Bendamustine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.3206
    Comments
    MethodCochran-Mantel-Haenszel
    Comments
    6. Secondary Outcome
    TitleMinimal Residual Disease Negative Complete Response (CR) Rate
    DescriptionThe MRD-negative CR rate was defined as the percentage of participants who achieved CR and became MRD-negative as determined by flow cytometry. CR as per International Working Group (IWG) was complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population includes all participants who were randomized into the study.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants623661
    Number (95% Confidence Interval) [Percentage of Participants]
    1.6
    2.6%
    5.6
    15.6%
    4.9
    8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rituximab + Bendamustine, MEDI-551 4 mg/kg + Bendamustine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.3130
    Comments
    MethodCochran-Mantel-Haenszel
    Comments
    7. Secondary Outcome
    TitleTime to Response
    DescriptionTime to response was evaluated using the Kaplan-Meier method.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population includes all participants who were randomized into the study.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants623661
    Median (95% Confidence Interval) [Months]
    2.1
    1.9
    2.1
    8. Secondary Outcome
    TitleTime to Disease Progression (TTP)
    DescriptionTTP was defined as the time from onset of treatment with study drug until first evidence/diagnosis of progressive disease or - in the absence of any diagnosis of progressive disease - until the participant´s death.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population includes all participants who were randomized into the study.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants623661
    Median (95% Confidence Interval) [Months]
    15.4
    15.0
    16.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rituximab + Bendamustine, MEDI-551 4 mg/kg + Bendamustine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.9527
    Comments
    MethodLog Rank
    Comments
    9. Secondary Outcome
    TitleProgression Free Survival (PFS)
    DescriptionPFS was measured from the start of treatment with study drug until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population includes all participants who were randomized into the study.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants623661
    Median (95% Confidence Interval) [Months]
    14.8
    15.0
    16.1
    10. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS was determined as the time from the start of treatment with study drug until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population includes all participants who were randomized into the study.
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants623661
    Number (95% Confidence Interval) [Months]
    NA
    NA
    NA
    11. Secondary Outcome
    TitleNumber of Participants Who Developed Detectable Anti-drug Antibodies (ADA)
    DescriptionA participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.
    Time FrameFrom treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any investigational product. Participants whom ADA samples were available were analyzed for this outcome measure.
    Arm/Group TitleMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionMEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants3157
    Number [Participants]
    4
    6.5%
    8
    22.2%
    12. Secondary Outcome
    TitleTerminal Half Life (t1/2) of MEDI-551
    DescriptionTerminal phase elimination half-life (T1/2) was the time required for half of the drug to be eliminated from the serum.
    Time FramePre-infusion and 1 hour post infusion on Days 2 and 8, Days 15 and 22 of cycle 1

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any investigational product. Participants whom PK samples were available were analyzed for this outcome measure.
    Arm/Group TitleMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionMEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    Measure Participants1238
    Mean (Standard Deviation) [Day]
    17.2
    (9.56)
    22.0
    (14.4)

    Adverse Events

    Time FrameFrom start of study drug administration until 90 days after the last dose of study drug
    Adverse Event Reporting Description
    Arm/Group TitleRituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Arm/Group DescriptionRituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
    All Cause Mortality
    Rituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Rituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total19/60 (31.7%) 16/33 (48.5%) 19/57 (33.3%)
    Blood and lymphatic system disorders
    Abdominal lymphadenopathy0/60 (0%) 01/33 (3%) 10/57 (0%) 0
    Anaemia1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Febrile neutropenia6/60 (10%) 60/33 (0%) 02/57 (3.5%) 2
    Lymphadenopathy0/60 (0%) 01/33 (3%) 11/57 (1.8%) 1
    Neutropenia1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Thrombocytopenia0/60 (0%) 01/33 (3%) 11/57 (1.8%) 1
    Cardiac disorders
    Atrial fibrillation0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Atrioventricular block1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Cardiac failure1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Myocardial infarction0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Congenital, familial and genetic disorders
    Thyroglossal cyst1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Eye disorders
    Uveitis1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Gastrointestinal disorders
    Ascites0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Diarrhoea1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Intestinal obstruction0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Nausea1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Small intestinal obstruction1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Upper gastrointestinal haemorrhage1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Vomiting2/60 (3.3%) 20/33 (0%) 00/57 (0%) 0
    General disorders
    Asthenia1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Inflammation1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Systemic inflammatory response syndrome1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Immune system disorders
    Anaphylactic reaction0/60 (0%) 01/33 (3%) 11/57 (1.8%) 3
    Infections and infestations
    Abdominal infection0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Bronchitis1/60 (1.7%) 11/33 (3%) 11/57 (1.8%) 1
    Gastroenteritis norovirus1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Pneumonia1/60 (1.7%) 14/33 (12.1%) 51/57 (1.8%) 1
    Pneumonia pseudomonal0/60 (0%) 01/33 (3%) 10/57 (0%) 0
    Pneumonia viral1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Rhinovirus infection1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Sepsis3/60 (5%) 31/33 (3%) 10/57 (0%) 0
    Skin infection1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Viral myocarditis1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Injury, poisoning and procedural complications
    Infusion related reaction1/60 (1.7%) 15/33 (15.2%) 105/57 (8.8%) 14
    Investigations
    Haemoglobin decreased0/60 (0%) 01/33 (3%) 20/57 (0%) 0
    Platelet count decreased0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Metabolism and nutrition disorders
    Decreased appetite1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Dehydration1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Diabetes mellitus0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Tumour lysis syndrome0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Bowen's disease1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Squamous cell carcinoma1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Nervous system disorders
    Coma0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Syncope1/60 (1.7%) 10/33 (0%) 01/57 (1.8%) 1
    Renal and urinary disorders
    Acute kidney injury1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Renal failure0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Reproductive system and breast disorders
    Female genital tract fistula1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Cough0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Dyspnoea1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Epistaxis0/60 (0%) 01/33 (3%) 10/57 (0%) 0
    Lung disorder1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Pneumonitis1/60 (1.7%) 20/33 (0%) 01/57 (1.8%) 1
    Respiratory failure0/60 (0%) 00/33 (0%) 01/57 (1.8%) 1
    Respiratory tract inflammation1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Vascular disorders
    Hypotension1/60 (1.7%) 10/33 (0%) 00/57 (0%) 0
    Other (Not Including Serious) Adverse Events
    Rituximab + BendamustineMEDI-551 2 mg/kg + BendamustineMEDI-551 4 mg/kg + Bendamustine
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total58/60 (96.7%) 31/33 (93.9%) 54/57 (94.7%)
    Blood and lymphatic system disorders
    Anaemia18/60 (30%) 647/33 (21.2%) 209/57 (15.8%) 13
    Febrile neutropenia4/60 (6.7%) 50/33 (0%) 01/57 (1.8%) 1
    Leukopenia3/60 (5%) 260/33 (0%) 01/57 (1.8%) 1
    Lymphopenia4/60 (6.7%) 263/33 (9.1%) 71/57 (1.8%) 5
    Neutropenia28/60 (46.7%) 7810/33 (30.3%) 4419/57 (33.3%) 58
    Thrombocytopenia12/60 (20%) 765/33 (15.2%) 810/57 (17.5%) 21
    Cardiac disorders
    Atrial fibrillation1/60 (1.7%) 12/33 (6.1%) 20/57 (0%) 0
    Tachycardia2/60 (3.3%) 21/33 (3%) 11/57 (1.8%) 1
    Ear and labyrinth disorders
    Vertigo2/60 (3.3%) 20/33 (0%) 01/57 (1.8%) 1
    Eye disorders
    Vision blurred1/60 (1.7%) 10/33 (0%) 02/57 (3.5%) 2
    Gastrointestinal disorders
    Abdominal discomfort3/60 (5%) 42/33 (6.1%) 21/57 (1.8%) 1
    Abdominal distension1/60 (1.7%) 12/33 (6.1%) 21/57 (1.8%) 1
    Abdominal pain7/60 (11.7%) 83/33 (9.1%) 37/57 (12.3%) 15
    Abdominal pain upper5/60 (8.3%) 61/33 (3%) 13/57 (5.3%) 3
    Constipation20/60 (33.3%) 239/33 (27.3%) 1110/57 (17.5%) 11
    Diarrhoea13/60 (21.7%) 205/33 (15.2%) 511/57 (19.3%) 15
    Dyspepsia1/60 (1.7%) 12/33 (6.1%) 24/57 (7%) 5
    Flatulence3/60 (5%) 31/33 (3%) 10/57 (0%) 0
    Gastrooesophageal reflux disease3/60 (5%) 40/33 (0%) 02/57 (3.5%) 2
    Gingival pain1/60 (1.7%) 11/33 (3%) 11/57 (1.8%) 1
    Haemorrhoids2/60 (3.3%) 20/33 (0%) 01/57 (1.8%) 1
    Nausea29/60 (48.3%) 4513/33 (39.4%) 2329/57 (50.9%) 47
    Vomiting13/60 (21.7%) 147/33 (21.2%) 87/57 (12.3%) 7
    General disorders
    Asthenia20/60 (33.3%) 314/33 (12.1%) 47/57 (12.3%) 17
    Chest discomfort2/60 (3.3%) 20/33 (0%) 02/57 (3.5%) 2
    Chills11/60 (18.3%) 156/33 (18.2%) 77/57 (12.3%) 10
    Fatigue18/60 (30%) 3814/33 (42.4%) 1920/57 (35.1%) 30
    Oedema peripheral3/60 (5%) 42/33 (6.1%) 37/57 (12.3%) 7
    Peripheral swelling1/60 (1.7%) 21/33 (3%) 21/57 (1.8%) 2
    Pyrexia20/60 (33.3%) 2711/33 (33.3%) 1414/57 (24.6%) 23
    Hepatobiliary disorders
    Hyperbilirubinaemia0/60 (0%) 02/33 (6.1%) 21/57 (1.8%) 2
    Immune system disorders
    Cytokine release syndrome0/60 (0%) 01/33 (3%) 12/57 (3.5%) 2
    Hypogammaglobulinaemia1/60 (1.7%) 11/33 (3%) 11/57 (1.8%) 2
    Infections and infestations
    Bronchitis4/60 (6.7%) 43/33 (9.1%) 44/57 (7%) 4
    Conjunctivitis2/60 (3.3%) 20/33 (0%) 01/57 (1.8%) 1
    Lung infection2/60 (3.3%) 21/33 (3%) 11/57 (1.8%) 1
    Nasopharyngitis3/60 (5%) 52/33 (6.1%) 34/57 (7%) 5
    Pneumonia0/60 (0%) 01/33 (3%) 14/57 (7%) 5
    Rhinitis2/60 (3.3%) 22/33 (6.1%) 20/57 (0%) 0
    Sinusitis3/60 (5%) 31/33 (3%) 16/57 (10.5%) 6
    Upper respiratory tract infection4/60 (6.7%) 43/33 (9.1%) 41/57 (1.8%) 1
    Urinary tract infection3/60 (5%) 80/33 (0%) 01/57 (1.8%) 3
    Injury, poisoning and procedural complications
    Contusion1/60 (1.7%) 10/33 (0%) 03/57 (5.3%) 3
    Infusion related reaction14/60 (23.3%) 2521/33 (63.6%) 6437/57 (64.9%) 123
    Investigations
    Alanine aminotransferase increased1/60 (1.7%) 30/33 (0%) 03/57 (5.3%) 4
    Aspartate aminotransferase increased1/60 (1.7%) 40/33 (0%) 03/57 (5.3%) 4
    Blood alkaline phosphatase increased1/60 (1.7%) 31/33 (3%) 22/57 (3.5%) 2
    Blood creatinine increased1/60 (1.7%) 12/33 (6.1%) 31/57 (1.8%) 1
    Blood lactate dehydrogenase increased4/60 (6.7%) 70/33 (0%) 00/57 (0%) 0
    Gamma-glutamyltransferase increased1/60 (1.7%) 41/33 (3%) 12/57 (3.5%) 2
    Lymphocyte count decreased3/60 (5%) 80/33 (0%) 02/57 (3.5%) 2
    Neutrophil count decreased9/60 (15%) 161/33 (3%) 33/57 (5.3%) 6
    Platelet count decreased2/60 (3.3%) 42/33 (6.1%) 22/57 (3.5%) 2
    Weight decreased5/60 (8.3%) 61/33 (3%) 10/57 (0%) 0
    White blood cell count decreased3/60 (5%) 31/33 (3%) 12/57 (3.5%) 2
    Metabolism and nutrition disorders
    Decreased appetite13/60 (21.7%) 174/33 (12.1%) 46/57 (10.5%) 6
    Dehydration1/60 (1.7%) 13/33 (9.1%) 30/57 (0%) 0
    Hyperglycaemia4/60 (6.7%) 42/33 (6.1%) 31/57 (1.8%) 1
    Hyperkalaemia2/60 (3.3%) 21/33 (3%) 12/57 (3.5%) 3
    Hyperuricaemia3/60 (5%) 55/33 (15.2%) 62/57 (3.5%) 2
    Hypoalbuminaemia2/60 (3.3%) 30/33 (0%) 02/57 (3.5%) 2
    Hypocalcaemia3/60 (5%) 31/33 (3%) 11/57 (1.8%) 1
    Hypokalaemia6/60 (10%) 71/33 (3%) 14/57 (7%) 4
    Hypomagnesaemia2/60 (3.3%) 22/33 (6.1%) 21/57 (1.8%) 1
    Hyponatraemia2/60 (3.3%) 21/33 (3%) 10/57 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia7/60 (11.7%) 71/33 (3%) 14/57 (7%) 4
    Back pain5/60 (8.3%) 54/33 (12.1%) 45/57 (8.8%) 8
    Bone pain4/60 (6.7%) 41/33 (3%) 15/57 (8.8%) 9
    Muscle spasms5/60 (8.3%) 91/33 (3%) 17/57 (12.3%) 9
    Muscular weakness3/60 (5%) 30/33 (0%) 01/57 (1.8%) 1
    Musculoskeletal chest pain0/60 (0%) 02/33 (6.1%) 22/57 (3.5%) 2
    Musculoskeletal pain2/60 (3.3%) 22/33 (6.1%) 22/57 (3.5%) 2
    Myalgia3/60 (5%) 60/33 (0%) 04/57 (7%) 5
    Neck pain1/60 (1.7%) 12/33 (6.1%) 22/57 (3.5%) 2
    Pain in extremity4/60 (6.7%) 42/33 (6.1%) 33/57 (5.3%) 3
    Nervous system disorders
    Dizziness5/60 (8.3%) 53/33 (9.1%) 67/57 (12.3%) 10
    Dysgeusia5/60 (8.3%) 73/33 (9.1%) 31/57 (1.8%) 1
    Headache7/60 (11.7%) 96/33 (18.2%) 95/57 (8.8%) 6
    Neuropathy peripheral1/60 (1.7%) 11/33 (3%) 11/57 (1.8%) 1
    Paraesthesia3/60 (5%) 30/33 (0%) 01/57 (1.8%) 2
    Restless legs syndrome2/60 (3.3%) 21/33 (3%) 11/57 (1.8%) 1
    Sciatica1/60 (1.7%) 10/33 (0%) 02/57 (3.5%) 3
    Psychiatric disorders
    Anxiety5/60 (8.3%) 50/33 (0%) 04/57 (7%) 5
    Depression2/60 (3.3%) 23/33 (9.1%) 32/57 (3.5%) 2
    Insomnia6/60 (10%) 72/33 (6.1%) 25/57 (8.8%) 5
    Renal and urinary disorders
    Dysuria4/60 (6.7%) 50/33 (0%) 00/57 (0%) 0
    Haematuria0/60 (0%) 02/33 (6.1%) 21/57 (1.8%) 1
    Pollakiuria1/60 (1.7%) 11/33 (3%) 12/57 (3.5%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough11/60 (18.3%) 135/33 (15.2%) 919/57 (33.3%) 24
    Dysphonia1/60 (1.7%) 12/33 (6.1%) 20/57 (0%) 0
    Dyspnoea9/60 (15%) 132/33 (6.1%) 24/57 (7%) 5
    Dyspnoea exertional3/60 (5%) 41/33 (3%) 10/57 (0%) 0
    Epistaxis1/60 (1.7%) 11/33 (3%) 12/57 (3.5%) 2
    Nasal congestion3/60 (5%) 41/33 (3%) 13/57 (5.3%) 4
    Oropharyngeal pain1/60 (1.7%) 11/33 (3%) 12/57 (3.5%) 2
    Pleural effusion1/60 (1.7%) 12/33 (6.1%) 21/57 (1.8%) 1
    Pulmonary congestion1/60 (1.7%) 20/33 (0%) 02/57 (3.5%) 2
    Rhinorrhoea3/60 (5%) 31/33 (3%) 13/57 (5.3%) 3
    Upper-airway cough syndrome2/60 (3.3%) 20/33 (0%) 01/57 (1.8%) 1
    Skin and subcutaneous tissue disorders
    Dry skin2/60 (3.3%) 22/33 (6.1%) 22/57 (3.5%) 2
    Erythema4/60 (6.7%) 40/33 (0%) 06/57 (10.5%) 6
    Hyperhidrosis7/60 (11.7%) 73/33 (9.1%) 32/57 (3.5%) 3
    Night sweats5/60 (8.3%) 61/33 (3%) 10/57 (0%) 0
    Pruritus9/60 (15%) 135/33 (15.2%) 96/57 (10.5%) 6
    Rash4/60 (6.7%) 74/33 (12.1%) 68/57 (14%) 10
    Rash erythematous3/60 (5%) 30/33 (0%) 00/57 (0%) 0
    Rash pruritic1/60 (1.7%) 10/33 (0%) 03/57 (5.3%) 3
    Vascular disorders
    Flushing4/60 (6.7%) 72/33 (6.1%) 31/57 (1.8%) 1
    Hypotension4/60 (6.7%) 42/33 (6.1%) 26/57 (10.5%) 7

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

    Results Point of Contact

    Name/TitleAstraZeneca Clinical Study Information Center
    OrganizationAstraZeneca
    Phone1-877-240-9479
    Emailinformation.center@astrazenca.com
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT01466153
    Other Study ID Numbers:
    • CD-ON-MEDI-551-1019
    First Posted:
    Nov 6, 2011
    Last Update Posted:
    May 31, 2017
    Last Verified:
    Apr 1, 2017