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NCT01776840 · ADVERSE EVENTS

Adverse events

A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma · Source last updated 2025-07-08

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Adverse events occurred during the study; they are not necessarily caused by treatment. Serious events are not interchangeable with severe/grade 3–4 events. These safety populations may differ from efficacy populations.

Collection time frame
All-cause mortality: From randomization (Day -3) up to 121 months; SAEs and Non SAEs: Placebo + BR (Treatment A): From first dose of study treatment (Day 1) up to 100.1 months; Ibrutinib + BR (Treatment B): From first dose of study treatment (Day 1) up to 117.2 months
Other-event reporting threshold
5%

All-cause mortality: All randomized participants. SAEs and Non SAEs: Safety analysis set included all randomized participants who received at least 1 dose of study drug (ibrutinib or placebo).

Participants affected / participants at risk, as reported
Safety groupSerious eventsOther eventsDeaths
Placebo + Bendamustine and Rituximab (BR) (Treatment A)

Participants received 4 capsules of ibrutinib-matching Placebo administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end, whichever occurred first. All participants also received a maximum of 6 cycles of BR background therapy (bendamustine hydrochloride 90 milligrams per meter square \[mg/m\^2\] intravenous \[IV\] infusion on Days 1 and 2 of each cycle and rituximab 375 mg/m\^2 IV infusion on Day 1 of each cycle), unless disease progression or unacceptable toxicity prior to Cycle 6. Participants with a complete response (CR) or partial response (PR) continued to receive background therapy with rituximab maintenance (375 mg/m\^2 IV infusion) on Day 1 every second cycle starting at Cycle 8 for a maximum of 12 additional doses unless disease progression or unacceptable toxicity. Each cycle was of 28 days. Participants received treatment A up to 100.1 months. After treatment unblinding at the time of the primary analysis, participants randomized to Treatment A discontinued placebo treatment.

157 / 260255 / 260129 / 262
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)

Participants received ibrutinib capsules 560 mg (4\*140 mg capsule) administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end, whichever occurred first. All participants also received a maximum of 6 cycles of BR background therapy (bendamustine hydrochloride 90 mg/m\^2 IV infusion on Days 1 and 2 of each cycle and rituximab 375 mg/m\^2 IV infusion on Day 1 of each cycle), unless disease progression or unacceptable toxicity prior to Cycle 6. Participants with a CR or PR continued to receive background therapy with rituximab maintenance (375 mg/m\^2 IV infusion) on Day 1 every second cycle starting at Cycle 8 for a maximum of 12 additional doses unless disease progression or unacceptable toxicity. Each cycle was of 28 days. Participants received treatment B up to 117.2 months. After treatment unblinding at the time of the primary analysis, participants randomized to Treatment B continued treatment with ibrutinib at the discretion of the investigator.

201 / 259256 / 259120 / 261

Group identifiers: EG000: Placebo + Bendamustine and Rituximab (BR) (Treatment A) · EG001: Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)

Serious adverse events

Event terms and counts are source-reported; expand to read more. A reporting threshold may omit less frequent events.

  1. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      3
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      5
      num At Risk
      259
    term
    Anaemia
  2. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      9
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      16
      num At Risk
      259
    term
    Febrile Neutropenia
  3. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      0
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Leukocytosis
  4. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      3
      num At Risk
      259
    term
    Lymphadenitis
  5. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      0
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Methaemoglobinaemia
  6. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      3
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      3
      num At Risk
      259
    term
    Neutropenia
  7. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      0
      num At Risk
      259
    term
    Pancytopenia
  8. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      0
      num At Risk
      259
    term
    Splenic Infarction
  9. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      3
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      2
      num At Risk
      259
    term
    Thrombocytopenia
  10. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      0
      num At Risk
      259
    term
    Acute Coronary Syndrome
  11. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      4
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Acute Myocardial Infarction
  12. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      0
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Angina Pectoris

Other reported adverse events

Event terms and counts are source-reported; expand to read more. A reporting threshold may omit less frequent events.

  1. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      60
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      83
      num At Risk
      259
    term
    Anaemia
  2. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      14
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      27
      num At Risk
      259
    term
    Leukopenia
  3. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      14
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      18
      num At Risk
      259
    term
    Lymphopenia
  4. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      104
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      109
      num At Risk
      259
    term
    Neutropenia
  5. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      43
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      62
      num At Risk
      259
    term
    Thrombocytopenia
  6. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      14
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      32
      num At Risk
      259
    term
    Atrial Fibrillation
  7. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      13
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      9
      num At Risk
      259
    term
    Palpitations
  8. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Ear and labyrinth disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      13
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      11
      num At Risk
      259
    term
    Vertigo
  9. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Eye disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      17
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      21
      num At Risk
      259
    term
    Cataract
  10. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Eye disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      5
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      16
      num At Risk
      259
    term
    Dry Eye
  11. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Eye disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      10
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      14
      num At Risk
      259
    term
    Vision Blurred
  12. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Gastrointestinal disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      29
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      25
      num At Risk
      259
    term
    Abdominal Pain
Complete source fields
description
All-cause mortality: All randomized participants. SAEs and Non SAEs: Safety analysis set included all randomized participants who received at least 1 dose of study drug (ibrutinib or placebo).
event Groups
  1. deaths Num Affected
    129
    deaths Num At Risk
    262
    description
    Participants received 4 capsules of ibrutinib-matching Placebo administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end, whichever occurred first. All participants also received a maximum of 6 cycles of BR background therapy (bendamustine hydrochloride 90 milligrams per meter square \[mg/m\^2\] intravenous \[IV\] infusion on Days 1 and 2 of each cycle and rituximab 375 mg/m\^2 IV infusion on Day 1 of each cycle), unless disease progression or unacceptable toxicity prior to Cycle 6. Participants with a complete response (CR) or partial response (PR) continued to receive background therapy with rituximab maintenance (375 mg/m\^2 IV infusion) on Day 1 every second cycle starting at Cycle 8 for a maximum of 12 additional doses unless disease progression or unacceptable toxicity. Each cycle was of 28 days. Participants received treatment A up to 100.1 months. After treatment unblinding at the time of the primary analysis, participants randomized to Treatment A discontinued placebo treatment.
    id
    EG000
    other Num Affected
    255
    other Num At Risk
    260
    serious Num Affected
    157
    serious Num At Risk
    260
    title
    Placebo + Bendamustine and Rituximab (BR) (Treatment A)
  2. deaths Num Affected
    120
    deaths Num At Risk
    261
    description
    Participants received ibrutinib capsules 560 mg (4\*140 mg capsule) administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end, whichever occurred first. All participants also received a maximum of 6 cycles of BR background therapy (bendamustine hydrochloride 90 mg/m\^2 IV infusion on Days 1 and 2 of each cycle and rituximab 375 mg/m\^2 IV infusion on Day 1 of each cycle), unless disease progression or unacceptable toxicity prior to Cycle 6. Participants with a CR or PR continued to receive background therapy with rituximab maintenance (375 mg/m\^2 IV infusion) on Day 1 every second cycle starting at Cycle 8 for a maximum of 12 additional doses unless disease progression or unacceptable toxicity. Each cycle was of 28 days. Participants received treatment B up to 117.2 months. After treatment unblinding at the time of the primary analysis, participants randomized to Treatment B continued treatment with ibrutinib at the discretion of the investigator.
    id
    EG001
    other Num Affected
    256
    other Num At Risk
    259
    serious Num Affected
    201
    serious Num At Risk
    259
    title
    Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
frequency Threshold
5
other Events
  1. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      60
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      83
      num At Risk
      259
    term
    Anaemia
  2. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      14
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      27
      num At Risk
      259
    term
    Leukopenia
  3. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      14
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      18
      num At Risk
      259
    term
    Lymphopenia
  4. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      104
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      109
      num At Risk
      259
    term
    Neutropenia
  5. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      43
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      62
      num At Risk
      259
    term
    Thrombocytopenia
  6. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      14
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      32
      num At Risk
      259
    term
    Atrial Fibrillation
  7. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      13
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      9
      num At Risk
      259
    term
    Palpitations
  8. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Ear and labyrinth disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      13
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      11
      num At Risk
      259
    term
    Vertigo
  9. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Eye disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      17
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      21
      num At Risk
      259
    term
    Cataract
  10. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Eye disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      5
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      16
      num At Risk
      259
    term
    Dry Eye
  11. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Eye disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      10
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      14
      num At Risk
      259
    term
    Vision Blurred
  12. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Gastrointestinal disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      29
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      25
      num At Risk
      259
    term
    Abdominal Pain
serious Events
  1. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      3
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      5
      num At Risk
      259
    term
    Anaemia
  2. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      9
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      16
      num At Risk
      259
    term
    Febrile Neutropenia
  3. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      0
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Leukocytosis
  4. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      3
      num At Risk
      259
    term
    Lymphadenitis
  5. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      0
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Methaemoglobinaemia
  6. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      3
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      3
      num At Risk
      259
    term
    Neutropenia
  7. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      0
      num At Risk
      259
    term
    Pancytopenia
  8. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      0
      num At Risk
      259
    term
    Splenic Infarction
  9. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Blood and lymphatic system disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      3
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      2
      num At Risk
      259
    term
    Thrombocytopenia
  10. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      1
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      0
      num At Risk
      259
    term
    Acute Coronary Syndrome
  11. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      4
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Acute Myocardial Infarction
  12. assessment Type
    NON_SYSTEMATIC_ASSESSMENT
    organ System
    Cardiac disorders
    source Vocabulary
    MedDRA Version 26.0
    stats
    1. group Id
      EG000
      num Affected
      0
      num At Risk
      260
    2. group Id
      EG001
      num Affected
      1
      num At Risk
      259
    term
    Angina Pectoris
time Frame
All-cause mortality: From randomization (Day -3) up to 121 months; SAEs and Non SAEs: Placebo + BR (Treatment A): From first dose of study treatment (Day 1) up to 100.1 months; Ibrutinib + BR (Treatment B): From first dose of study treatment (Day 1) up to 117.2 months

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