Clinical Trial Results:
A Confirmatory Multicenter, Single-arm Study to Assess the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (BLAST)
Summary
|
|
EudraCT number |
2010-018314-75 |
Trial protocol |
DE BE GB AT ES CZ FR PL IT NL |
Global end of trial date |
07 Jan 2019
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
02 Jan 2020
|
First version publication date |
02 Jan 2020
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
MT103-203
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01207388 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Amgen Inc.
|
||
Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
|
||
Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
|
||
Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
07 Jan 2019
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
07 Jan 2019
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The purpose of this study is to confirm whether the bispecific T cell engager blinatumomab (MT103) is effective, safe and tolerable in the treatment of ALL patients with minimal residual disease.
|
||
Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines, the GCPs applicable to all regions where the study was conducted and in accordance with the ethical principles set forth in the Declaration of Helsinki.
The study protocol and all amendments, the informed consent form, and any accompanying materials provided to subjects were reviewed and approved by an Independent Ethics Committee (IEC), at each center/country.
The investigator or his/her designee informed the subject of all aspects pertaining to the subject’s participation in the study before any screening procedures were performed.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Nov 2010
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 12
|
||
Country: Number of subjects enrolled |
Netherlands: 1
|
||
Country: Number of subjects enrolled |
Romania: 3
|
||
Country: Number of subjects enrolled |
Spain: 5
|
||
Country: Number of subjects enrolled |
United Kingdom: 7
|
||
Country: Number of subjects enrolled |
Austria: 4
|
||
Country: Number of subjects enrolled |
Belgium: 10
|
||
Country: Number of subjects enrolled |
Czech Republic: 1
|
||
Country: Number of subjects enrolled |
Germany: 56
|
||
Country: Number of subjects enrolled |
Italy: 15
|
||
Country: Number of subjects enrolled |
Russian Federation: 2
|
||
Worldwide total number of subjects |
116
|
||
EEA total number of subjects |
114
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
101
|
||
From 65 to 84 years |
15
|
||
85 years and over |
0
|
|
|||||||||||||
Recruitment
|
|||||||||||||
Recruitment details |
This study was conducted at 46 centers in Austria, Belgium, Czech Republic, France, Germany, Italy, Netherlands, Romania, Russia, Spain, and the United Kingdom. | ||||||||||||
Pre-assignment
|
|||||||||||||
Screening details |
This study enrolled adults with a diagnosis of minimal residual disease (MRD; ≥ 10^-3 leukemic cells) -positive B-precursor acute lymphoblastic leukemia (ALL) who were in complete hematologic remission. A total of 211 subjects were screened; 116 subjects received at least 1 infusion of blinatumomab and were included in the full analysis set (FAS). | ||||||||||||
Period 1
|
|||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
Arms
|
|||||||||||||
Arm title
|
Blinatumomab | ||||||||||||
Arm description |
Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate of 15 μg/m²/day over 28 days followed by an infusion-free period of 14 days for up to 4 cycles of treatment. Participants suitable for allogeneic hematopoietic stem cell transplant (HSCT) after treatment with at least 1 cycle of blinatumomab may have undergone allogeneic HSCT instead of receiving further cycles with blinatumomab. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Blinatumomab
|
||||||||||||
Investigational medicinal product code |
MT103
|
||||||||||||
Other name |
BLINCYTO™
|
||||||||||||
Pharmaceutical forms |
Powder for solution for infusion
|
||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||
Dosage and administration details |
Administered by continuous intravenous infusion at a constant flow rate of 15 μg/m²/day over 28 days.
|
||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Blinatumomab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate of 15 μg/m²/day over 28 days followed by an infusion-free period of 14 days for up to 4 cycles of treatment. Participants suitable for allogeneic hematopoietic stem cell transplant (HSCT) after treatment with at least 1 cycle of blinatumomab may have undergone allogeneic HSCT instead of receiving further cycles with blinatumomab. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Blinatumomab
|
||
Reporting group description |
Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate of 15 μg/m²/day over 28 days followed by an infusion-free period of 14 days for up to 4 cycles of treatment. Participants suitable for allogeneic hematopoietic stem cell transplant (HSCT) after treatment with at least 1 cycle of blinatumomab may have undergone allogeneic HSCT instead of receiving further cycles with blinatumomab. | ||
Subject analysis set title |
Cycle 1 MRD 10^-5
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with an MRD level 10^-5 at the end of cycle 1.
|
||
Subject analysis set title |
Cycle 1 MRD 10^-4
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with an MRD level 10^-4 at the end of cycle 1.
|
||
Subject analysis set title |
Cycle 1 MRD 10^-3
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with an MRD level 10^-3 at the end of cycle 1.
|
||
Subject analysis set title |
Cycle 1 MRD 10^-1
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with an MRD level 10^-1 at the end of cycle 1.
|
||
Subject analysis set title |
Cycle 1 MRD Unknown
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with an unknown MRD level at the end of cycle 1.
|
|
|||||||||
End point title |
Percentage of Participants With a Minimal Residual Disease (MRD) Response Within the First Treatment Cycle [1] | ||||||||
End point description |
At the end of the first treatment cycle (Day 29) a bone marrow aspiration/biopsy was performed and evaluated by the central MRD laboratory.
Complete MRD response is defined as no polymerase chain reaction (PCR) amplification of individual rearrangements of immunoglobulin (Ig)- or T-cell receptor (TCR)-genes detected after completion of the first cycle.
The analysis was conducted using the primary endpoint full analysis set (Prim EP FAS), which included all participants with an Ig TCR PCR MRD assay with the minimum required sensitivity of 1 x 10^-4 at central lab established at Baseline.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
During the first cycle (6 weeks)
|
||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This was a single-arm study. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Hematological Relapse-free Survival (RFS) | ||||||||
End point description |
Hematological RFS was measured from first dose of blinatumomab until the first assessment of documented relapse (either hematological or extramedullary), secondary leukemia, or death due to any cause. Participants without documented relapse or death were censored at the time of their last hematological assessment. Participants who received chemotherapy for relapsed or persistent MRD or for any other reason, or HSCT after blinatumomab treatment, before relapse or death occurred, were censored at the start of chemotherapy or HSCT, respectively.
Hematological relapse was defined as unequivocal detection of > 5% leukemia cells in bone marrow as measured by cytological, microscopic assessment, presence of circulating leukemia blasts, or extramedullary leukemia, whichever occurred first. The 18-month Kaplan-Meier estimate of hematological RFS is reported.
Analysis is based on FAS participants in hematological complete remission at treatment start, excluding Philadelphia-positive subjects.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
18 months, up to the data cut-off date of 05 August 2015
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Overall Survival | ||||||||
End point description |
Overall survival was measured from the first treatment with blinatumomab until death due to any cause. Participants who did not die were censored at their last contact date.
The analysis was conducted in the FAS. "99999" indicates data not estimable at the time of analysis due to the low number of events.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant | ||||||||
End point description |
The mortality rate within 100 days after allogeneic HSCT was defined as the Kaplan-Meier estimate of the percentage of participants dying within 100 days after the day of the first allogeneic HSCT.
The analysis was based on FAS participants who underwent HSCT prior to relapse (hematological or extramedullary) excluding Philadelphia-positive participants.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
100 days after HSCT, as of the data cut-off date of 05 August 2015
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Time to Hematological Relapse | ||||||||
End point description |
Time to hematological relapse was measured from the start of treatment with blinatumomab until hematological or extramedullary relapse. Participants who died or received HSCT or post-blinatumomab chemotherapy after treatment with blinatumomab were censored at their last hematological assessment prior to death or HSCT or post-blinatumomab chemotherapy (whichever occurred first).
The analysis was based on FAS participants who were in hematological complete remission at treatment start, excluding Philadelphia-positive participants. "99999" indicates data not estimable due to the low number of events.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Duration of Complete MRD Response | ||||||||
End point description |
Duration of MRD response was analyzed as the time from onset of MRD negativity until MRD or hematological relapse or date of last confirmation of negative MRD status. Participants who received chemotherapy or HSCT after treatment with blinatumomab before hematological or extramedullary relapse were censored at the start of chemotherapy or HSCT, respectively.
MRD relapse is defined as the reappearance of individual rearrangements of Ig- or TCR-genes ≥ lower limit of quantification (LLOQ) for at least 1 individual marker measured by an assay with a sensitivity of minimum 10^-4.
Hematological relapse is defined as the unequivocal detection of > 5% leukemia cells in bone marrow as measured by cytological or microscopic assessment, presence of circulating leukemia blasts, or extramedullary leukemia.
The analysis was based on FAS participants in hematological complete remission at treatment start, excluding Philadelphia-positive participants, who had an MRD complete response at cycle 1.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change in MRD Level From Baseline to End of Cycle 1 in Non-MRD Responders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
MRD level was measured by polymerase chain reaction (PCR) performed on bone marrow and assessed by the central laboratory. An MRD level of 10^-n corresponds to residual leukemia cells at a frequency of 1 per 10ⁿ bone marrow cells.
The analysis was conducted in FAS participants who were in hematological complete remission at treatment start, with no MRD Response in the first treatment cycle, excluding Philadelphia-positive participants.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and end of cycle 1 (6 weeks)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Number of Participants With Adverse Events | ||||||||||||||||||||||||||||||
End point description |
Adverse events (AEs) were evaluated for severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4, as follows:
Grade 1 - Mild AE;
Grade 2 - Moderate AE;
Grade 3 - Severe AE;
Grade 4 - Life-threatening or disabling AE;
Grade 5 - Death.
The investigator used medical judgment to determine if there was a causal relationship (ie, related, unrelated) between an adverse event and blinatumomab.
An AE was considered "serious" if it resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions, was a congenital anomaly or birth defect or was a medically important condition.
Safety analyses were conducted in all participants who received any infusion of blinatumomab.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
From the first dose of blinatumomab until 30 days after last dose; the median treatment duration was 55 days.
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||
End point title |
Maximum Change From Baseline in EORTC-QLQ-C30 Scales in Cycles 1 to 4 | ||||||||||||||||||||||||||||||||||||||
End point description |
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea, Financial Impact).
For each of these scales, scores range from 0 to 100. For the GHS and 5 functional scales a high score indicates better global health status/functioning and a positive change from baseline indicates improvement. For the 9 symptom scales, a high score indicates a higher level of symptoms, and a negative change from Baseline indicates an improvement in symptoms.
The maximum changes from baseline to cycles 1 through 4 in each domain are reported, in the full analysis set (FAS).
|
||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and day 29 of treatment cycles 1 - 4
|
||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
Notes [2] - n = subjects included in the calculation of each scale at the time point of maximum change. |
|||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in EORTC-QLQ-C30 Scales at the End of the Core Study | ||||||||||||||||||||||||||||||||||||||
End point description |
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea, Financial Impact).
For each of these scales, scores range from 0 to 100. For the GHS and 5 functional scales a high score indicates better global health status/functioning and a positive change from baseline indicates improvement. For the 9 symptom scales, a high score indicates a higher level of symptoms, and a negative change from Baseline indicates an improvement in symptoms.
|
||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and 30 days after end of the last infusion (end of the core study, a maximum of 26 weeks).
|
||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
Notes [3] - Full analysis set with available data |
|||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Maximum Change From Baseline in EuroQoL 5-Dimension (EQ-5D) Scales During Cycles 1 to 4 | ||||||||||||||||||
End point description |
The EQ-5D is a self-administered questionnaire which captures 3 basic types of information: a descriptive profile (health state index) and the overall health rating using a visual analog scale. The health state index measures mobility, self-care, usual activities, pain/discomfort and anxiety/depression on scales from no problems (score = 1), some problems (score = 2), to extreme problems (score = 3). For each dimension the mean change from baseline was calculated at the end of each treatment cycle and at the end of the core study. The maximum observed change from baseline during cycles 1 to 4 are reported for each dimension in the FAS.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline and day 29 of treatment cycles 1 - 4
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [4] - n = subjects included in the calculation of each scale at the time point of maximum change |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change From Baseline in EuroQoL 5-Dimension (EQ-5D) Scales at the End of the Core Study | ||||||||||||||||||
End point description |
The EQ-5D is a self-administered questionnaire which captures 3 basic types of information: a descriptive profile (health state index) and the overall health rating using a visual analog scale. The health state index measures mobility, self-care, usual activities, pain/discomfort and anxiety/depression on scales from no problems (score = 1), some problems (score = 2), to extreme problems (score = 3). For each dimension the mean change from baseline was calculated at the end of each treatment cycle and at the end of the core study.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline and 30 days after end of the last infusion (end of the core study, a maximum of 26 weeks).
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [5] - Full analysis set with available data |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Resource Utilization: Number of Participants Reporting Use of Transfusion of Blood Products | ||||||||||||||||||
End point description |
Resource utilization was analyzed in all participants in the FAS.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Resource Utilization: Duration of Hospitalization | ||||||||
End point description |
Resource utilization was analyzed in all participants in the FAS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months.
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From the first dose of blinatumomab until 30 days after last dose; the median treatment duration was 55 days.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Blinatumomab [15 ug/m2/d]
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate of 15 µg/m²/day over 28 days followed by an infusion-free period of 14 days for up to 4 cycles of treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
04 Feb 2011 |
- Update storage and stability information
- Update to labeling information |
||
04 Jul 2011 |
- Add collection of blinatumomab immunogenicity sample
- Update known and potential benefits and risks
- Implement prescreening for early detection of MRD
- Update MRD assay requirements
- Update inclusion criteria #4 (diagnosis of ALL)
- Update labeling information
- Update storage and stability information
- Update preparation of drug product
- Update safety follow-up for subjects who undergo HSCT
- Update early termination
- Update definitions in drug safety
- Add information regarding legal and ethical requirements and protocol amendments
- Clarify the following: duration of subject participation, intense chemotherapy, informed consent, writing test, examination of CSF, selected sites for ECG and PK assessments
- Implement minor administrative changes and update references and contacts |
||
17 Feb 2012 |
- Add a provision to implement additional urgent safety measures in case of neurologic-related adverse events
- Change contact details for drug safety department and safe reporting
- Adapt patient information and informed consent form |
||
11 Jul 2012 |
- Update assessment schedule
- Update list of contacts
- Update known and potential benefits and risks
- Add a provision to restart drug at a lower dose in the case of neurologic-related adverse events
- Add C-reactive Protein testing
- Clarify the following: retreatment cycles, efficacy assessments, hospitalization, discontinuation criteria, use of premedication, MRD sample requirements, assessment for neurologic-relate adverse events, reporting periods for adverse events, safety reporting procedures |
||
06 Mar 2014 |
- Amend the key secondary objective/endpoint |
||
13 Jun 2014 |
- Harmonize the description of the blinatumomab and its preparation with the Investigator's Brochure and other clinical trials within the blinatumomab clinical development program |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/29358182 |