INTELLANCE-2: Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas
Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02343406
Collaborator
European Organisation for Research and Treatment of Cancer - EORTC (Other)
266
102
5
52.2
2.6
0
Study Details
Study Description
Brief Summary
This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The study objectives were to assess whether depatuxizumab mafodotin (ABT-414) alone or in combination with temozolomide (TMZ) improved overall survival (OS), progression-free survival (PFS), tumor response, quality of life, neurological deterioration-free survival (NDFS), and steroid use compared to standard treatment with lomustine single agent or TMZ re-challenge in adult subjects ≥ 18 years of age with centrally-confirmed recurrent epidermal growth factor receptor (EGFR)-amplified glioblastoma. The safety, pharmacokinetics, and efficacy of depatuxizumab mafodotin in children <18 years of age was evaluated in a pediatric substudy. The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.
Study Design
Study Type:
Interventional
Actual Enrollment
:
266 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
INTELLANCE-2: ABT-414 Alone or ABT-414 Plus Temozolomide Versus Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group
Actual Study Start Date
:
Feb 17, 2015
Actual Primary Completion Date
:
Jun 24, 2019
Actual Study Completion Date
:
Jun 24, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ABT-414/temozolomide Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants |
Drug: Depatuxizumab mafodotin
Adults: intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).
Other Names:
Drug: Temozolomide
Capsules administered orally, 150 mg/m^2 on Days 1-5 for the first 28-day cycle, with dose escalation to 200 mg/m^2 in subsequent cycles in case of adequate tolerance until one of the treatment withdrawal criteria was met.
Other Names:
|
| Experimental: ABT-414_adult Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants |
Drug: Depatuxizumab mafodotin
Adults: intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).
Other Names:
|
| Active Comparator: Control_lomustine Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year. |
Drug: Lomustine
Capsules administered orally, 110 mg/m^2 on Day 1 of every 42-day treatment period. Treatment continued until one of the treatment withdrawal criteria was met, for a maximum of one year.
Other Names:
|
| Active Comparator: Control_ temozolomide Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. |
Drug: Temozolomide
Capsules administered orally, 150 mg/m^2 on Days 1-5 for the first 28-day cycle, with dose escalation to 200 mg/m^2 in subsequent cycles in case of adequate tolerance until one of the treatment withdrawal criteria was met.
Other Names:
|
| Experimental: ABT-414_ pediatric Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
Drug: Depatuxizumab mafodotin
Adults: intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Adult Study: Overall Survival (OS) [From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months.]
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine).
- Adult Study: Progression-Free Survival (PFS) [Measured every 8 weeks from date of randomization until the date of first objective progression or subject's death, whichever occurred first, up to 2 years]
Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse.
- Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug [From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks]
The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)
- Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414 [Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose]
Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
- Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF [Samples collected Cycle 1 Days 1, 2, 3, 5, 8]
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin.
- Pediatric Study: Half-life (t1/2) Observed for ABT-414 [Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose]
Half-life is the calculated time it takes for half of the drug to leave the body.
- Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF [Samples collected Cycle 1 Days 1, 2, 3, 5, 8]
Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin.
- Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414 [Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose]
AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
- Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF [Samples collected Cycle 1 Days 1, 2, 3, 5, 8]
AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Secondary Outcome Measures
- Adult Study: Objective Response Rate (ORR) [Every 8 weeks at each assessment of disease, up to 28 months]
The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder.
- Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation [From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months]
Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation.
- Pediatric Study: Objective Response Rate (ORR) [Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks]
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
- Pediatric Study: Best Tumor Response Rate [Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks]
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
- Pediatric Study: Duration of Response [Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks]
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
- Pediatric Study: Overall Survival [From the date of enrollment to the date of death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months]
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
- Pediatric Study: Time to Progression [Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks]
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study.
- Pediatric Study: Progression-Free Survival [Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks]
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
- Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning [Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually]
The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Adult participants (greater than or equal to 18 years old):
-
Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
-
In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy
-
Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
-
Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification
-
Presence of EGFR amplification confirmed by central assessment; participants with undetermined EGFR status are excluded
-
World Health Organization (WHO) Performance status 0 - 2
-
No more than one line of chemotherapy (concurrent and adjuvant Temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
-
Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
-
Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.
-
Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula.
-
Liver function: bilirubin < 1.5× upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) < 2.5× ULN
Pediatric sub-study participants (less than 18 years old):
-
Histologically proven high grade glioma (HGG: WHO grade III glioma [e.g anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma], grade IV glioma [e.g. glioblastoma, gliosarcoma] or diffuse intrinsic pontine glioma [DIPG]).
-
Must either have recurrent/progressive tumor or, if newly diagnosed, have completed any planned radiation therapy at least 4 weeks prior to first dose of ABT-414.
-
The tumor tissue must have been determined to have EGFR amplification, (by local or other testing service).
-
Availability of adequate biological material for retrospective confirmatory central testing of EGFR amplification
-
Participant has sufficiently recovered from previous therapy. The investigator believes that benefit of treating the pediatric subject with ABT-414 outweighs the expected risks and that this treatment is in the best interests of the pediatric subject.
-
Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula for pediatric patients ≥12 years of age and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m^2 by modified Schwartz equation for pediatric patients < 12 years of age.
-
Liver function: Total bilirubin ≤ 1.5× upper limit of the normal range (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) <= 3× ULN. Participants with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is < 3 times ULN. Not allowed are participants with known chronic liver disease and/or cirrhosis.
Exclusion Criteria:
Adult population (greater than or equal to 18 years old):
-
Prior treatment with nitrosoureas
-
Prior treatment with bevacizumab
-
Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents
-
Prior discontinuation of temozolomide chemotherapy for toxicity reasons
-
Prior Radiation Therapy (RT) with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
-
Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
-
Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
-
No history of wheat allergies and Coeliac disease.
-
No EIAED, patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization.
Pediatric sub-study (less than 18 years old):
-
(For recurrent disease) No prior RT with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
-
No current or recent (within 4 weeks or 5 half-lives [whichever is shorter] before enrollment) treatment with another investigational drug
-
Female participants of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lucile Packard Children's Hosp /ID# 153678 | Palo Alto | California | United States | 34304 |
| 2 | Children's Hospital Colorado /ID# 153677 | Aurora | Colorado | United States | 80045 |
| 3 | Univ of Colorado Cancer Center /ID# 134882 | Aurora | Colorado | United States | 80045 |
| 4 | Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798 | Denver | Colorado | United States | 80218 |
| 5 | Rush University Medical Center /ID# 137542 | Chicago | Illinois | United States | 60612 |
| 6 | Dana-Farber Cancer Institute /ID# 154210 | Boston | Massachusetts | United States | 02215 |
| 7 | Long Island Brain Tumor Center /ID# 134496 | Lake Success | New York | United States | 11042 |
| 8 | Weill Cornell Medicine /ID# 152656 | New York | New York | United States | 10032-3725 |
| 9 | Cleveland Clinic Main Campus /ID# 137540 | Cleveland | Ohio | United States | 44195 |
| 10 | University of Pittsburgh MC /ID# 134491 | Pittsburgh | Pennsylvania | United States | 15260 |
| 11 | Tennessee Oncology, PLLC /ID# 134492 | Nashville | Tennessee | United States | 37203 |
| 12 | UT Southwestern Medical Center /ID# 136718 | Dallas | Texas | United States | 75390-7208 |
| 13 | Swedish Medical Center /ID# 136719 | Seattle | Washington | United States | 98104 |
| 14 | Port Macquarie Base Hospital /ID# 134569 | Port Macquarie | New South Wales | Australia | 2444 |
| 15 | Sydney Children's Hospital /ID# 153533 | Randwick | New South Wales | Australia | 2031 |
| 16 | Royal North Shore Hospital /ID# 147092 | Saint Leonards | New South Wales | Australia | 2065 |
| 17 | Calvary Mater Newcastle /ID# 134570 | Waratah | New South Wales | Australia | 2298 |
| 18 | Southern Medical Day Care Ctr /ID# 134495 | Wollongong | New South Wales | Australia | 2500 |
| 19 | Royal Brisbane and Women's Hospital /ID# 147091 | Herston | Queensland | Australia | 4029 |
| 20 | Royal Adelaide Hospital /ID# 135208 | Adelaide | South Australia | Australia | 5000 |
| 21 | Royal Hobart Hospital /ID# 135209 | Hobart | Tasmania | Australia | 7000 |
| 22 | Barwon Health University Hospital Geelong /ID# 134493 | Geelong | Victoria | Australia | 3220 |
| 23 | Royal Children's Hospital /ID# 157624 | Melbourne | Victoria | Australia | 3052 |
| 24 | University Hospital St. Polten /ID# 139070 | St. Pölten | Niederoesterreich | Austria | 3100 |
| 25 | LKH-Univ. Klinikum Graz /ID# 139071 | Graz | Austria | 8036 | |
| 26 | Kepler Universitätsklinikum GmbH - Neuromed Campus /ID# 139068 | Linz | Austria | 4020 | |
| 27 | Cliniques Universitaires Saint Luc /ID# 139391 | Woluwe-Saint-Lambert | Bruxelles-Capitale | Belgium | 1200 |
| 28 | Grand Hôpital de Charleroi /ID# 139342 | Charleroi | Hainaut | Belgium | 6000 |
| 29 | UZ Gent /ID# 152944 | Gent | Oost-Vlaanderen | Belgium | 9000 |
| 30 | AZ St-Jan Brugge-Oostende AV /ID# 137927 | Brugge | West-Vlaanderen | Belgium | 8000 |
| 31 | ZNA Middelheim /ID# 137926 | Antwerp | Belgium | 2020 | |
| 32 | UZ Leuven /ID# 137925 | Leuven | Belgium | 3000 | |
| 33 | Montreal Neurological Institut /ID# 136309 | Montreal | Quebec | Canada | H3A 2B4 |
| 34 | Fakultni Nemocnice v Motole /ID# 139509 | Prague 5 | Praha 5 | Czechia | 150 06 |
| 35 | Masarykuv onkologikcy ustav /ID# 139508 | Brno | Czechia | 656 53 | |
| 36 | FN Hradec Kralove /ID# 139510 | Hradec Kralove | Czechia | 500 05 | |
| 37 | Univ Hosp Ostrava-Poruba /ID# 139507 | Ostrava | Czechia | 708 52 | |
| 38 | Helsinki Univ Central Hospital /ID# 140078 | Helsinki | Finland | 00290 | |
| 39 | Helsinki Univ Central Hospital /ID# 153069 | Helsinki | Finland | 00290 | |
| 40 | Turku University Hospital /ID# 140861 | Turku | Finland | 20520 | |
| 41 | CHRU Lille - Hôpital Claude Huriez /ID# 137916 | Lille CEDEX | Hauts-de-France | France | 59045 |
| 42 | Centre Oscar Lambret /ID# 169619 | Lille | Hauts-de-France | France | 59020 |
| 43 | CHU-Hopital Avicenne /ID# 137910 | Bobigny | Ile-de-France | France | 93000 |
| 44 | Gustave Roussy /ID# 137912 | Villejuif | Ile-de-France | France | 94805 |
| 45 | Institut de Cancer de l'Ouest /ID# 137914 | St Herblain CEDEX | Loire-Atlantique | France | 44805 |
| 46 | Hopital de la Timone /ID# 137911 | Marseille CEDEX 05 | Provence-Alpes-Cote-d Azur | France | 13385 |
| 47 | CHU de Nice /ID# 137917 | Nice CEDEX 1 | Provence-Alpes-Cote-d Azur | France | 06002 |
| 48 | Centre Leon Berard /ID# 137918 | Lyon CEDEX 08 | Rhone | France | 69373 |
| 49 | Institut de Cancer de l'Ouest /ID# 137909 | Angers | France | 49055 | |
| 50 | Hospices Civils de Lyon /ID# 137913 | Bron | France | 69500 | |
| 51 | Hopital Pitie Salpetriere /ID# 145887 | Paris | France | 75651 | |
| 52 | Universitaetsklinik Heidelberg /ID# 137924 | Heidelberg | Baden-Wuerttemberg | Germany | 69120 |
| 53 | Universitatsklinik Regensburg /ID# 137920 | Ratisbon | Bayern | Germany | 93053 |
| 54 | Univ Klinik Eppendorf Hamburg /ID# 137921 | Hamburg | Germany | 20246 | |
| 55 | LMU Klinikum der Universität München /ID# 137922 | Munich | Germany | 80337 | |
| 56 | Universitatsklinikum Tubingen /ID# 137923 | Tuebingen | Germany | 72076 | |
| 57 | Pecsi Tudomanyegyetem /ID# 136111 | Pécs | Pecs | Hungary | 7624 |
| 58 | Semmelweis Egyetem /ID# 152578 | Budapest | Hungary | 1085 | |
| 59 | National Institute of Oncology /ID# 135970 | Budapest | Hungary | 1122 | |
| 60 | Orszagos Klinikai Idegtudomany /ID# 135971 | Budapest | Hungary | 1145 | |
| 61 | Debreceni Egyetem Klinikai Központ /ID# 135969 | Debrecen | Hungary | 4032 | |
| 62 | Cork University Hospital /ID# 136828 | Cork | Ireland | T12 E8YV | |
| 63 | Beaumont Hospital /ID# 136829 | Dublin | Ireland | D09 XR63 | |
| 64 | Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335 | Bologna | Italy | 40139 | |
| 65 | Ospedale Generale di Bolzano /ID# 138338 | Bolzano | Italy | 39100 | |
| 66 | Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395 | Milan | Italy | 20133 | |
| 67 | Istituto Oncologico Veneto /ID# 138336 | Padova | Italy | 35128 | |
| 68 | Azienda Ospedaliera Sant' Andrea /ID# 138337 | Rome | Italy | 00189 | |
| 69 | Seoul National Univ Bundang ho /ID# 136841 | Seongnam | Gyeonggido | Korea, Republic of | 13620 |
| 70 | Samsung Medical Center /ID# 136842 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 06351 |
| 71 | Seoul National University Hospital /ID# 136840 | Seoul | Korea, Republic of | 03080 | |
| 72 | Hospital Zambrano Hellion /ID# 138076 | San Pedro Garza García | Mexico | 66278 | |
| 73 | Vrije Universiteit Medisch Centrum /ID# 137221 | Amsterdam | Netherlands | 1081 HV | |
| 74 | Universitair Medisch Centrum Groningen /ID# 138266 | Groningen | Netherlands | 9713 GZ | |
| 75 | Erasmus Medisch Centrum /ID# 136981 | Rotterdam | Netherlands | 3015 CE | |
| 76 | Haaglanden Medisch Centrum /ID# 137222 | The Hague | Netherlands | 2512 VA | |
| 77 | Universitair Medisch Centrum Utrecht /ID# 137219 | Utrecht | Netherlands | 3584 CX | |
| 78 | Prinses Maxima Centrum /ID# 204409 | Utrecht | Netherlands | 3584 EA | |
| 79 | Uniwersyteckie Centrum Kliniczne /ID# 137919 | Gdansk | Mazowieckie | Poland | 80-214 |
| 80 | Wojewodzkie Wielospecjalistycz /ID# 137654 | Lodz | Poland | 93-509 | |
| 81 | National University Hospital /ID# 135951 | Singapore | Singapore | 119074 | |
| 82 | National Cancer Ctr Singapore /ID# 135952 | Singapore | Singapore | 169610 | |
| 83 | KK Women's & Children Hospital /ID# 153676 | Singapore | Singapore | 229899 | |
| 84 | Instituto Catalán de Oncología (ICO) Badalona /ID# 140976 | Badalona | Barcelona | Spain | 08916 |
| 85 | Clinica Universitar de Navarra - Pamplona /ID# 140047 | Pamplona | Navarra, Comunidad | Spain | 31008 |
| 86 | Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688 | Barcelona | Spain | 08908 | |
| 87 | Hospital Universitario Nino /ID# 153800 | Madrid | Spain | 28009 | |
| 88 | Hosp Univ 12 de Octubre /ID# 137908 | Madrid | Spain | 28041 | |
| 89 | Centre Hospitalier Univ Vaudoi /ID# 137929 | Lausanne | Switzerland | 1011 | |
| 90 | University Hospital Zurich /ID# 137930 | Zurich | Switzerland | 8091 | |
| 91 | China Medical University Hosp /ID# 136976 | Taichung City | Taichung | Taiwan | 40447 |
| 92 | National Taiwan Univ Hosp /ID# 136975 | Taipei City | Taipei | Taiwan | 10002 |
| 93 | Taichung Veterans General Hosp /ID# 136977 | Taichung City | Taiwan | 40705 | |
| 94 | Taipei Veterans General Hosp /ID# 136974 | Taipei City | Taiwan | 11217 | |
| 95 | Linkou Chang Gung Memorial Ho /ID# 136944 | Taoyuan City | Taiwan | 33305 | |
| 96 | Guy's and St Thomas' NHS Found /ID# 140312 | London | London, City Of | United Kingdom | SE1 9RT |
| 97 | Univ Hospitals Birmingham NHS Foundation trust /ID# 136978 | Birmingham | United Kingdom | B15 2TG | |
| 98 | Gartnavel General Hospital /ID# 136979 | Glasgow | United Kingdom | G12 0YN | |
| 99 | Hull and East Yorkshire NHS /ID# 136917 | Hull | United Kingdom | HU8 9HE | |
| 100 | University College Hospitals /ID# 136879 | London | United Kingdom | NW1 2BU | |
| 101 | Great Ormond St Hospital NHS /ID# 153421 | London | United Kingdom | WC1N 3JH | |
| 102 | Christie NHS Foundation Trust /ID# 140313 | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- AbbVie
- European Organisation for Research and Treatment of Cancer - EORTC
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02343406
Other Study ID Numbers:
- M14-483
- 2014-004438-24
- EORTC 1410-BTG
First Posted:
Jan 22, 2015
Last Update Posted:
May 22, 2020
Last Verified:
May 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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 AbbVie
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Intention-to-treat population (ITT): all randomized participants. Nine enrolled adult participants did not have a screen failure form reported and were not randomized. In the table below, "Completed" and "Not completed" refer to study drug treatment, and the reasons not completed listings refer to study drug treatment. |
| Arm/Group Title | ABT-414/Temozolomide | ABT-414_adult | Control_lomustine | Control_ Temozolomide | ABT-414_ Pediatric |
|---|---|---|---|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants | Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year. | Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Period Title: Overall Study | |||||
| STARTED | 88 | 86 | 60 | 26 | 6 |
| COMPLETED | 0 | 0 | 2 | 0 | 1 |
| NOT COMPLETED | 88 | 86 | 58 | 26 | 5 |
Baseline Characteristics
| Arm/Group Title | ABT-414/Temozolomide | ABT-414_adult | Control_lomustine | Control_ Temozolomide | ABT-414_ Pediatric | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants | Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year. | Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). | Total of all reporting groups |
| Overall Participants | 88 | 86 | 60 | 26 | 6 | 266 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
57.9
(8.15)
|
58.1
(9.18)
|
57.8
(10.62)
|
55.9
(11.04)
|
10.5
(5.43)
|
56.7
(11.65)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
29
33%
|
36
41.9%
|
19
31.7%
|
9
34.6%
|
5
83.3%
|
98
36.8%
|
| Male |
59
67%
|
50
58.1%
|
41
68.3%
|
17
65.4%
|
1
16.7%
|
168
63.2%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
8
9.1%
|
7
8.1%
|
5
8.3%
|
2
7.7%
|
0
0%
|
22
8.3%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
16
18.2%
|
6
7%
|
12
20%
|
4
15.4%
|
3
50%
|
41
15.4%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Reported |
0
0%
|
0
0%
|
0
0%
|
1
3.8%
|
0
0%
|
1
0.4%
|
| Missing |
64
72.7%
|
73
84.9%
|
43
71.7%
|
19
73.1%
|
3
50%
|
202
75.9%
|
Outcome Measures
| Title | Adult Study: Overall Survival (OS) |
|---|---|
| Description | Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine). |
| Time Frame | From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized adult participants; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined. |
| Arm/Group Title | ABT-414/Temozolomide | ABT-414_adult | Control (Temozolomide/Lomustine) |
|---|---|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants | Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. |
| Measure Participants | 88 | 86 | 86 |
| 25th quartile |
5.7
|
4.6
|
4.9
|
| 50th quartile |
9.6
|
7.9
|
8.2
|
| 75th quartile |
16.9
|
15.5
|
12.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ABT-414/Temozolomide, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle). | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.062 |
| Comments | 2-sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.71 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 1.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ABT-414_adult, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle). | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.835 |
| Comments | 2-sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.04 | |
| Confidence Interval |
(2-Sided) 95% 0.73 to 1.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adult Study: Progression-Free Survival (PFS) |
|---|---|
| Description | Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse. |
| Time Frame | Measured every 8 weeks from date of randomization until the date of first objective progression or subject's death, whichever occurred first, up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized adult participants; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined. |
| Arm/Group Title | ABT-414/Temozolomide | ABT-414_adult | Control (Temozolomide/Lomustine) |
|---|---|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants | Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. |
| Measure Participants | 88 | 86 | 86 |
| 25th quartile |
1.8
|
1.5
|
1.6
|
| 50th quartile |
2.7
|
1.9
|
1.9
|
| 75th quartile |
4.9
|
3.5
|
4.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ABT-414/Temozolomide, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.123 |
| Comments | 2-sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 95% 0.55 to 1.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ABT-414_adult, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.117 |
| Comments | 2-sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.31 | |
| Confidence Interval |
(2-Sided) 95% 0.93 to 1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug |
|---|---|
| Description | The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0) |
| Time Frame | From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric participants (safety population) |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 6 |
| Number [percentage of participants] |
100
113.6%
|
| Title | Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414 |
|---|---|
| Description | Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose. |
| Time Frame | Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric participants with available data |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 5 |
| Mean (Standard Deviation) [µg/mL] |
31.4
(15.0)
|
| Title | Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF |
|---|---|
| Description | Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin. |
| Time Frame | Samples collected Cycle 1 Days 1, 2, 3, 5, 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric participants with available data |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 5 |
| Mean (Standard Deviation) [ng/mL] |
0.272
(0.0983)
|
| Title | Pediatric Study: Half-life (t1/2) Observed for ABT-414 |
|---|---|
| Description | Half-life is the calculated time it takes for half of the drug to leave the body. |
| Time Frame | Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric participants with available data |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 4 |
| Mean (Standard Deviation) [days] |
9.0
(1.5)
|
| Title | Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF |
|---|---|
| Description | Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin. |
| Time Frame | Samples collected Cycle 1 Days 1, 2, 3, 5, 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric participants with available data |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 2 |
| Mean (Standard Deviation) [days] |
11.2
(22.9)
|
| Title | Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414 |
|---|---|
| Description | AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population. |
| Time Frame | Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric participants with available data |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 5 |
| Mean (Standard Deviation) [µg*h/mL] |
3170
(1320)
|
| Title | Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF |
|---|---|
| Description | AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population. |
| Time Frame | Samples collected Cycle 1 Days 1, 2, 3, 5, 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric participants with available data |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 5 |
| Mean (Standard Deviation) [ng*h/mL] |
14.1
(6.22)
|
| Title | Adult Study: Objective Response Rate (ORR) |
|---|---|
| Description | The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder. |
| Time Frame | Every 8 weeks at each assessment of disease, up to 28 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with measurable disease at baseline; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined. |
| Arm/Group Title | ABT-414/Temozolomide | ABT-414_adult | Control (Temozolomide/Lomustine) |
|---|---|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants | Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. |
| Measure Participants | 49 | 39 | 45 |
| Number (95% Confidence Interval) [percentage of participants] |
14.3
16.3%
|
7.7
9%
|
4.4
7.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ABT-414/Temozolomide, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | Comparison is based on Cochran-Mantel-Haenszel method with stratification factors. Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle). | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.06 |
| Comments | 2-sided | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 3.1 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 16.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ABT-414_adult, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | Comparison is based on Cochran-Mantel-Haenszel method with stratification factors. Stratified at randomization by regions of the world (North America, Europe and Australia, Asia/Other Regions), WHO performance status (0, > 0), timing of relapse (< 16 weeks, ≥ 16 weeks after first day of last TMZ cycle). | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.767 |
| Comments | 2-sided | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.21 | |
| Confidence Interval |
(2-Sided) 95% 0.12 to 12.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation |
|---|---|
| Description | Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation. |
| Time Frame | From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized adult participants with EGFRvIII-mutated tumors; participants in the control arms were treated based on the time of relapse and they differ in prognostic profile, therefore data were combined. |
| Arm/Group Title | ABT-414/Temozolomide | ABT-414_adult | Control (Temozolomide/Lomustine) |
|---|---|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants | Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle who received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year OR adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle who received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. |
| Measure Participants | 39 | 36 | 47 |
| 25th quartile |
6.3
|
5.0
|
4.7
|
| 50th quartile |
9.4
|
8.4
|
7.5
|
| 75th quartile |
14.4
|
13.9
|
12.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ABT-414/Temozolomide, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.127 |
| Comments | 2-sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.67 | |
| Confidence Interval |
(2-Sided) 95% 0.4 to 1.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ABT-414_adult, Control (Temozolomide/Lomustine) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.64 |
| Comments | 2-sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.52 to 1.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pediatric Study: Objective Response Rate (ORR) |
|---|---|
| Description | The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study. |
| Time Frame | Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric efficacy data were not collected |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 0 |
| Title | Pediatric Study: Best Tumor Response Rate |
|---|---|
| Description | The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study. |
| Time Frame | Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric efficacy data were not collected |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 0 |
| Title | Pediatric Study: Duration of Response |
|---|---|
| Description | The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study. |
| Time Frame | Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric efficacy data were not collected |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 0 |
| Title | Pediatric Study: Overall Survival |
|---|---|
| Description | The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study. |
| Time Frame | From the date of enrollment to the date of death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric efficacy data were not collected |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 0 |
| Title | Pediatric Study: Time to Progression |
|---|---|
| Description | The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study. |
| Time Frame | Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric efficacy data were not collected |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 0 |
| Title | Pediatric Study: Progression-Free Survival |
|---|---|
| Description | The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study. |
| Time Frame | Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric efficacy data were not collected |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 0 |
| Title | Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning |
|---|---|
| Description | The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study. |
| Time Frame | Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pediatric efficacy data were not collected |
| Arm/Group Title | ABT-414_ Pediatric |
|---|---|
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 35 days (adults) or 49 days (pediatric subjects) after the last dose of study drug, up to 125 weeks. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Serious and non-serious adverse events occurring after the subject signed the study-specific informed consent and prior to the initial dose of study drug were to be collected only if they were considered by the Investigator to be causally related to required study procedures. | |||||||||
| Arm/Group Title | ABT-414/Temozolomide | ABT-414_adult | Control_lomustine | Control_ Temozolomide | ABT-414_ Pediatric | |||||
| Arm/Group Description | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult subjects | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult subjects | Adult subjects relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year. | Adult subjects relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement). | |||||
All Cause Mortality |
||||||||||
| ABT-414/Temozolomide | ABT-414_adult | Control_lomustine | Control_ Temozolomide | ABT-414_ Pediatric | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 80/88 (90.9%) | 80/84 (95.2%) | 52/56 (92.9%) | 21/21 (100%) | 5/6 (83.3%) | |||||
Serious Adverse Events |
||||||||||
| ABT-414/Temozolomide | ABT-414_adult | Control_lomustine | Control_ Temozolomide | ABT-414_ Pediatric | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 39/88 (44.3%) | 30/84 (35.7%) | 19/56 (33.9%) | 5/21 (23.8%) | 3/6 (50%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| FEBRILE NEUTROPENIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| THROMBOCYTOPENIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||
| VERTIGO | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Eye disorders | ||||||||||
| CORNEAL EPITHELIAL MICROCYSTS | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| ABDOMINAL PAIN | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| CONSTIPATION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| DIARRHOEA | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| DIVERTICULAR PERFORATION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 1/21 (4.8%) | 2 | 0/6 (0%) | 0 |
| NAUSEA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| VOMITING | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 1/6 (16.7%) | 4 |
| General disorders | ||||||||||
| DISEASE PROGRESSION | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| FATIGUE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| GENERAL PHYSICAL HEALTH DETERIORATION | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| PYREXIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| Hepatobiliary disorders | ||||||||||
| HEPATIC STEATOSIS | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Infections and infestations | ||||||||||
| DIVERTICULITIS | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| LOWER RESPIRATORY TRACT INFECTION | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| MENINGITIS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| PNEUMONIA | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| RESPIRATORY TRACT INFECTION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| RESPIRATORY TRACT INFECTION VIRAL | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SEPSIS | 1/88 (1.1%) | 2 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| URINARY TRACT INFECTION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 2 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| WOUND INFECTION | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| CLAVICLE FRACTURE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| FALL | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 1/56 (1.8%) | 3 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| FEMORAL NECK FRACTURE | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HIP FRACTURE | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HUMERUS FRACTURE | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| LUMBAR VERTEBRAL FRACTURE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| PELVIC FRACTURE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 2 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Investigations | ||||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| BODY TEMPERATURE INCREASED | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| DECREASED APPETITE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| DEHYDRATION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HYPERGLYCAEMIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HYPONATRAEMIA | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| ARTHRALGIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| BACK PAIN | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| MUSCULAR WEAKNESS | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| MALIGNANT NEOPLASM PROGRESSION | 11/88 (12.5%) | 16 | 7/84 (8.3%) | 10 | 2/56 (3.6%) | 4 | 2/21 (9.5%) | 2 | 2/6 (33.3%) | 2 |
| METASTASES TO PERITONEUM | 0/88 (0%) | 0 | 1/84 (1.2%) | 3 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| NEOPLASM PROGRESSION | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| TUMOUR HAEMORRHAGE | 1/88 (1.1%) | 2 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Nervous system disorders | ||||||||||
| APHASIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| APRAXIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| BRAIN OEDEMA | 2/88 (2.3%) | 2 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| CEREBROVASCULAR ACCIDENT | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| EPILEPSY | 0/88 (0%) | 0 | 1/84 (1.2%) | 2 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| GENERALISED TONIC-CLONIC SEIZURE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HAEMORRHAGE INTRACRANIAL | 0/88 (0%) | 0 | 2/84 (2.4%) | 3 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HEADACHE | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 3 |
| HEMIPARESIS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HEMIPLEGIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| HYDROCEPHALUS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| MUSCLE SPASTICITY | 2/88 (2.3%) | 2 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| NERVOUS SYSTEM DISORDER | 0/88 (0%) | 0 | 2/84 (2.4%) | 2 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| NEUROLOGICAL DECOMPENSATION | 0/88 (0%) | 0 | 3/84 (3.6%) | 3 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| PARTIAL SEIZURES | 1/88 (1.1%) | 2 | 2/84 (2.4%) | 2 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SEIZURE | 9/88 (10.2%) | 9 | 3/84 (3.6%) | 3 | 4/56 (7.1%) | 4 | 1/21 (4.8%) | 1 | 0/6 (0%) | 0 |
| STATUS EPILEPTICUS | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SUBDURAL HYGROMA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SYNCOPE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| TRANSIENT ISCHAEMIC ATTACK | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| COMPLETED SUICIDE | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| CONFUSIONAL STATE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SUICIDAL IDEATION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SUICIDE ATTEMPT | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| NEPHROLITHIASIS | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| HYPOXIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| PNEUMONIA ASPIRATION | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| PNEUMONITIS | 1/88 (1.1%) | 2 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| PULMONARY EMBOLISM | 3/88 (3.4%) | 4 | 0/84 (0%) | 0 | 2/56 (3.6%) | 2 | 1/21 (4.8%) | 1 | 0/6 (0%) | 0 |
| RESPIRATORY FAILURE | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| Vascular disorders | ||||||||||
| DEEP VEIN THROMBOSIS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SUBGALEAL HAEMATOMA | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
| ABT-414/Temozolomide | ABT-414_adult | Control_lomustine | Control_ Temozolomide | ABT-414_ Pediatric | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 84/88 (95.5%) | 76/84 (90.5%) | 46/56 (82.1%) | 20/21 (95.2%) | 6/6 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| ANAEMIA | 7/88 (8%) | 7 | 4/84 (4.8%) | 13 | 5/56 (8.9%) | 7 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| LEUKOPENIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 5/56 (8.9%) | 11 | 1/21 (4.8%) | 4 | 0/6 (0%) | 0 |
| LYMPHOPENIA | 9/88 (10.2%) | 17 | 8/84 (9.5%) | 16 | 9/56 (16.1%) | 13 | 4/21 (19%) | 8 | 0/6 (0%) | 0 |
| NEUTROPENIA | 2/88 (2.3%) | 2 | 1/84 (1.2%) | 3 | 10/56 (17.9%) | 12 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| THROMBOCYTOPENIA | 19/88 (21.6%) | 55 | 7/84 (8.3%) | 11 | 19/56 (33.9%) | 34 | 8/21 (38.1%) | 11 | 0/6 (0%) | 0 |
| Cardiac disorders | ||||||||||
| BRADYCARDIA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| SINUS BRADYCARDIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| Ear and labyrinth disorders | ||||||||||
| EAR PAIN | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| Endocrine disorders | ||||||||||
| CUSHINGOID | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| Eye disorders | ||||||||||
| CATARACT | 4/88 (4.5%) | 4 | 5/84 (6%) | 5 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| CORNEAL EPITHELIAL MICROCYSTS | 25/88 (28.4%) | 64 | 12/84 (14.3%) | 22 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| CORNEAL OPACITY | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 3 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| DRY EYE | 20/88 (22.7%) | 36 | 22/84 (26.2%) | 33 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| EYE IRRITATION | 6/88 (6.8%) | 8 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 2 |
| EYE PAIN | 7/88 (8%) | 10 | 11/84 (13.1%) | 20 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| EYELID PTOSIS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| KERATITIS | 16/88 (18.2%) | 24 | 27/84 (32.1%) | 45 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| KERATOPATHY | 15/88 (17%) | 24 | 7/84 (8.3%) | 8 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 3/6 (50%) | 3 |
| LACRIMATION INCREASED | 9/88 (10.2%) | 10 | 3/84 (3.6%) | 5 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| OCULAR DISCOMFORT | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| PHOTOPHOBIA | 12/88 (13.6%) | 14 | 8/84 (9.5%) | 11 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 3/6 (50%) | 4 |
| PUNCTATE KERATITIS | 3/88 (3.4%) | 6 | 6/84 (7.1%) | 6 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| PUPILLARY REFLEX IMPAIRED | 0/88 (0%) | 0 | 2/84 (2.4%) | 3 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| VISION BLURRED | 30/88 (34.1%) | 52 | 17/84 (20.2%) | 27 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 2/6 (33.3%) | 5 |
| VISUAL IMPAIRMENT | 3/88 (3.4%) | 3 | 5/84 (6%) | 6 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| Gastrointestinal disorders | ||||||||||
| ABDOMINAL DISTENSION | 0/88 (0%) | 0 | 2/84 (2.4%) | 2 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| ABDOMINAL PAIN | 2/88 (2.3%) | 2 | 2/84 (2.4%) | 2 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| ABDOMINAL PAIN UPPER | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| CONSTIPATION | 23/88 (26.1%) | 28 | 8/84 (9.5%) | 9 | 2/56 (3.6%) | 2 | 6/21 (28.6%) | 6 | 0/6 (0%) | 0 |
| DIARRHOEA | 8/88 (9.1%) | 9 | 6/84 (7.1%) | 6 | 3/56 (5.4%) | 3 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 2 |
| NAUSEA | 21/88 (23.9%) | 33 | 8/84 (9.5%) | 8 | 6/56 (10.7%) | 6 | 6/21 (28.6%) | 7 | 2/6 (33.3%) | 3 |
| PROCTALGIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| VOMITING | 19/88 (21.6%) | 23 | 5/84 (6%) | 5 | 3/56 (5.4%) | 4 | 6/21 (28.6%) | 6 | 3/6 (50%) | 5 |
| General disorders | ||||||||||
| ASTHENIA | 6/88 (6.8%) | 9 | 3/84 (3.6%) | 4 | 4/56 (7.1%) | 7 | 2/21 (9.5%) | 2 | 1/6 (16.7%) | 1 |
| FATIGUE | 33/88 (37.5%) | 60 | 27/84 (32.1%) | 39 | 13/56 (23.2%) | 16 | 5/21 (23.8%) | 6 | 2/6 (33.3%) | 6 |
| GAIT DISTURBANCE | 4/88 (4.5%) | 5 | 3/84 (3.6%) | 5 | 2/56 (3.6%) | 2 | 2/21 (9.5%) | 2 | 1/6 (16.7%) | 1 |
| INFLUENZA LIKE ILLNESS | 4/88 (4.5%) | 4 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| OEDEMA PERIPHERAL | 7/88 (8%) | 9 | 2/84 (2.4%) | 2 | 4/56 (7.1%) | 5 | 4/21 (19%) | 4 | 0/6 (0%) | 0 |
| PYREXIA | 5/88 (5.7%) | 5 | 4/84 (4.8%) | 4 | 1/56 (1.8%) | 1 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| Infections and infestations | ||||||||||
| CONJUNCTIVITIS | 7/88 (8%) | 8 | 6/84 (7.1%) | 6 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| EYE INFECTION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| INFLUENZA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| NASOPHARYNGITIS | 5/88 (5.7%) | 6 | 1/84 (1.2%) | 1 | 3/56 (5.4%) | 3 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| ORAL CANDIDIASIS | 2/88 (2.3%) | 2 | 2/84 (2.4%) | 2 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| UPPER RESPIRATORY TRACT INFECTION | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| VAGINAL INFECTION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 2 |
| VULVOVAGINAL CANDIDIASIS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| FALL | 4/88 (4.5%) | 5 | 4/84 (4.8%) | 5 | 3/56 (5.4%) | 3 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| Investigations | ||||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 11/88 (12.5%) | 24 | 12/84 (14.3%) | 17 | 3/56 (5.4%) | 4 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 9/88 (10.2%) | 12 | 13/84 (15.5%) | 15 | 2/56 (3.6%) | 2 | 0/21 (0%) | 0 | 1/6 (16.7%) | 4 |
| BLOOD CULTURE POSITIVE | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | 4/88 (4.5%) | 6 | 8/84 (9.5%) | 15 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| LYMPHOCYTE COUNT DECREASED | 7/88 (8%) | 11 | 4/84 (4.8%) | 4 | 6/56 (10.7%) | 13 | 2/21 (9.5%) | 2 | 0/6 (0%) | 0 |
| NEUTROPHIL COUNT DECREASED | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 8/56 (14.3%) | 11 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 10 |
| PLATELET COUNT DECREASED | 21/88 (23.9%) | 46 | 9/84 (10.7%) | 17 | 15/56 (26.8%) | 31 | 2/21 (9.5%) | 6 | 1/6 (16.7%) | 29 |
| WEIGHT DECREASED | 4/88 (4.5%) | 4 | 7/84 (8.3%) | 9 | 3/56 (5.4%) | 4 | 0/21 (0%) | 0 | 3/6 (50%) | 8 |
| WEIGHT INCREASED | 6/88 (6.8%) | 8 | 6/84 (7.1%) | 9 | 3/56 (5.4%) | 3 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| WHITE BLOOD CELL COUNT DECREASED | 3/88 (3.4%) | 7 | 2/84 (2.4%) | 2 | 5/56 (8.9%) | 15 | 1/21 (4.8%) | 1 | 2/6 (33.3%) | 8 |
| Metabolism and nutrition disorders | ||||||||||
| DECREASED APPETITE | 10/88 (11.4%) | 11 | 5/84 (6%) | 7 | 2/56 (3.6%) | 2 | 0/21 (0%) | 0 | 1/6 (16.7%) | 2 |
| HYPERGLYCAEMIA | 5/88 (5.7%) | 8 | 3/84 (3.6%) | 3 | 1/56 (1.8%) | 1 | 1/21 (4.8%) | 1 | 0/6 (0%) | 0 |
| HYPERKALAEMIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 2/6 (33.3%) | 6 |
| HYPERMAGNESAEMIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| HYPOKALAEMIA | 7/88 (8%) | 12 | 2/84 (2.4%) | 2 | 1/56 (1.8%) | 1 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| ARTHRALGIA | 6/88 (6.8%) | 7 | 3/84 (3.6%) | 3 | 3/56 (5.4%) | 3 | 1/21 (4.8%) | 1 | 0/6 (0%) | 0 |
| BACK PAIN | 7/88 (8%) | 8 | 7/84 (8.3%) | 7 | 4/56 (7.1%) | 4 | 2/21 (9.5%) | 2 | 1/6 (16.7%) | 1 |
| MUSCLE SPASMS | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| MUSCULAR WEAKNESS | 4/88 (4.5%) | 4 | 3/84 (3.6%) | 3 | 2/56 (3.6%) | 2 | 2/21 (9.5%) | 2 | 0/6 (0%) | 0 |
| MUSCULOSKELETAL PAIN | 5/88 (5.7%) | 6 | 2/84 (2.4%) | 2 | 0/56 (0%) | 0 | 1/21 (4.8%) | 1 | 0/6 (0%) | 0 |
| PAIN IN EXTREMITY | 6/88 (6.8%) | 7 | 1/84 (1.2%) | 1 | 1/56 (1.8%) | 1 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 2 |
| PAIN IN JAW | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| Nervous system disorders | ||||||||||
| APHASIA | 9/88 (10.2%) | 10 | 9/84 (10.7%) | 10 | 3/56 (5.4%) | 3 | 3/21 (14.3%) | 3 | 0/6 (0%) | 0 |
| ATAXIA | 1/88 (1.1%) | 1 | 1/84 (1.2%) | 1 | 2/56 (3.6%) | 2 | 0/21 (0%) | 0 | 2/6 (33.3%) | 3 |
| BALANCE DISORDER | 2/88 (2.3%) | 3 | 1/84 (1.2%) | 1 | 3/56 (5.4%) | 3 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| DEPRESSED LEVEL OF CONSCIOUSNESS | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| DIZZINESS | 7/88 (8%) | 9 | 2/84 (2.4%) | 2 | 1/56 (1.8%) | 1 | 3/21 (14.3%) | 3 | 1/6 (16.7%) | 1 |
| DYSARTHRIA | 1/88 (1.1%) | 1 | 3/84 (3.6%) | 3 | 3/56 (5.4%) | 4 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| ENCEPHALOPATHY | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| HEADACHE | 21/88 (23.9%) | 31 | 20/84 (23.8%) | 21 | 8/56 (14.3%) | 8 | 2/21 (9.5%) | 2 | 2/6 (33.3%) | 3 |
| HEMIPARESIS | 2/88 (2.3%) | 2 | 7/84 (8.3%) | 7 | 7/56 (12.5%) | 9 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| HYDROCEPHALUS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| PERIPHERAL MOTOR NEUROPATHY | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 3/56 (5.4%) | 4 | 0/21 (0%) | 0 | 0/6 (0%) | 0 |
| SEIZURE | 6/88 (6.8%) | 13 | 7/84 (8.3%) | 11 | 5/56 (8.9%) | 9 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| SOMNOLENCE | 3/88 (3.4%) | 3 | 3/84 (3.6%) | 3 | 3/56 (5.4%) | 6 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| Psychiatric disorders | ||||||||||
| ANXIETY | 5/88 (5.7%) | 6 | 2/84 (2.4%) | 2 | 1/56 (1.8%) | 1 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| DEPRESSION | 4/88 (4.5%) | 4 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| DISINHIBITION | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| INSOMNIA | 8/88 (9.1%) | 10 | 6/84 (7.1%) | 7 | 2/56 (3.6%) | 2 | 2/21 (9.5%) | 2 | 0/6 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| URINARY INCONTINENCE | 1/88 (1.1%) | 1 | 3/84 (3.6%) | 3 | 3/56 (5.4%) | 3 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| COUGH | 5/88 (5.7%) | 7 | 2/84 (2.4%) | 2 | 3/56 (5.4%) | 3 | 3/21 (14.3%) | 3 | 2/6 (33.3%) | 2 |
| DYSPHONIA | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 1/56 (1.8%) | 1 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| DYSPNOEA | 8/88 (9.1%) | 8 | 1/84 (1.2%) | 1 | 1/56 (1.8%) | 1 | 1/21 (4.8%) | 1 | 0/6 (0%) | 0 |
| EPISTAXIS | 2/88 (2.3%) | 3 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| NASAL CONGESTION | 0/88 (0%) | 0 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 2/6 (33.3%) | 2 |
| OROPHARYNGEAL PAIN | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 1/21 (4.8%) | 1 | 1/6 (16.7%) | 1 |
| PRODUCTIVE COUGH | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| DERMATITIS DIAPER | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| DRY SKIN | 1/88 (1.1%) | 1 | 5/84 (6%) | 5 | 0/56 (0%) | 0 | 2/21 (9.5%) | 2 | 1/6 (16.7%) | 1 |
| ERYTHEMA | 1/88 (1.1%) | 1 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| HYPERKERATOSIS | 0/88 (0%) | 0 | 0/84 (0%) | 0 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| PRURITUS | 2/88 (2.3%) | 2 | 1/84 (1.2%) | 1 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
| RASH | 7/88 (8%) | 7 | 2/84 (2.4%) | 3 | 1/56 (1.8%) | 1 | 2/21 (9.5%) | 2 | 0/6 (0%) | 0 |
| Vascular disorders | ||||||||||
| HYPERTENSION | 9/88 (10.2%) | 18 | 6/84 (7.1%) | 9 | 4/56 (7.1%) | 5 | 1/21 (4.8%) | 1 | 0/6 (0%) | 0 |
| HYPOTENSION | 1/88 (1.1%) | 1 | 3/84 (3.6%) | 3 | 0/56 (0%) | 0 | 0/21 (0%) | 0 | 1/6 (16.7%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02343406
Other Study ID Numbers:
- M14-483
- 2014-004438-24
- EORTC 1410-BTG
First Posted:
Jan 22, 2015
Last Update Posted:
May 22, 2020
Last Verified:
May 1, 2020