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Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT01466179
First received: October 28, 2011
Last updated: July 12, 2016
Last verified: July 2016
Results First Received: December 21, 2014  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Acute Lymphoblastic Leukemia
Intervention: Biological: Blinatumomab

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

This study was open to adult patients with relapsed / refractory B-precursor acute lymphoblastic leukemia (ALL).

The study protocol originally used a Simon 2-stage design and was subsequently expanded to include a third stage. Protocol amendment 4 added an additional cohort of participants for central nervous system evaluations.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Two hundred twenty-five participants enrolled in the study overall. Results below include data for 189 participants enrolled in the first 3 stages of the study (the primary analysis set). An additional 36 participants enrolled in the Additional Evaluation Cohort are not reported here as the study is ongoing and data collection has not completed.

Reporting Groups
  Description
Blinatumomab Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.

Participant Flow:   Overall Study
    Blinatumomab
STARTED   189 [1] 
COMPLETED   10 [2] 
NOT COMPLETED   179 
Ongoing in core study                2 
Physician Decision                46 
Progressive disease                43 
Adverse Event                32 
Disease relapse                23 
Lack of Efficacy                14 
Death                7 
Withdrawal by Subject                7 
Protocol Violation                2 
Other                3 
[1] Participants enrolled during the first 3 stages of the study
[2] Completed 5 cycles of treatment; Data as of the time of the data cut-off date (10 October 2013).



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Primary Analysis Set

Reporting Groups
  Description
Blinatumomab Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.

Baseline Measures
   Blinatumomab 
Overall Participants Analyzed 
[Units: Participants]
 189 
Age 
[Units: Years]
Median (Full Range)
 39.0 
 (18 to 79) 
Age, Customized 
[Units: Participants]
 
18 to < 35 years   90 
35 to < 55 years   46 
55 to < 65 years   28 
≥ 65 years   25 
Gender 
[Units: Participants]
 
Female   70 
Male   119 
Race/Ethnicity, Customized [1] 
[Units: Participants]
 
White   145 
Asian   6 
Black or African American   7 
American Indian or Alaska native   1 
Native Hawaiian or other Pacific Islander   1 
Other   9 
Not recorded   20 
[1] Race was not permitted to be collected in France
Disease stage entry criteria met [1] 
[Units: Participants]
 
Primary refractory   16 
Relapse ≤ 12 months of allogeneic HSCT   39 
Entering first salvage; first remission ≤ 12 mo   23 
Entering second or greater salvage therapies   108 
No criteria met   3 
[1] HSCT = hematopoietic stem cell transplantation
Number of prior relapses 
[Units: Participants]
 
 16 
 107 
 46 
>2   20 
Prior allogeneic HSCT and prior relapses [1] 
[Units: Participants]
 
Prior allogeneic HSCT   64 
No prior alloHSCT, no prior relapse   16 
No prior alloHSCT, 1 prior relapse   84 
No prior alloHSCT, 2 prior relapses   22 
No prior alloHSCT, > 2 prior relapses   3 
[1] alloHSCT = allogeneic hematopoietic stem cell transplantation
Number of prior salvage therapies 
[Units: Participants]
 
No prior salvage therapy   38 
1 prior salvage therapy   77 
2 prior salvage therapies   42 
> 2 prior salvage therapies   32 
Time since initial diagnosis 
[Units: Months]
Median (Full Range)
 16.59 
 (1.9 to 249.0) 
Time since last relapse [1] 
[Units: Months]
Median (Full Range)
 1.38 
 (0.1 to 56.8) 
[1] Reported for 173 participants with a prior relapse (the other16 participants were primary refractory with no prior relapses).
Baseline bone marrow blast category [1] 
[Units: Participants]
 
< 10%   1 
10% - < 50%   43 
≥ 50%   145 
[1] Bone marrow blasts were assessed by local and central laboratories; reported data are based on maximum central and local laboratory assessments.


  Outcome Measures
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1.  Primary:   Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment   [ Time Frame: Within the first 2 cycles of treatment, 12 weeks ]

2.  Secondary:   Time to Hematological Relapse (Duration of Response)   [ Time Frame: Up to the data cut-off date of 10 October 2013; median observation time was 8.0 months. ]

3.  Secondary:   Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission   [ Time Frame: Up to the data cut-off date of 10 October 2013. Maximum duration on study was 17.8 months. ]

4.  Secondary:   Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment   [ Time Frame: Within the first 2 cycles of treatment, 12 weeks ]

5.  Secondary:   Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment   [ Time Frame: Within the first 2 cycles of treatment, 12 weeks ]

6.  Secondary:   Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment   [ Time Frame: Within the first 2 cycles of treatment, 12 weeks ]

7.  Secondary:   Relapse-free Survival   [ Time Frame: Up to the data cut-off date of 10 October 2013; median observation time was 8.9 months. ]

8.  Secondary:   Event-free Survival   [ Time Frame: Up to the data cut-off date of 10 October 2013; median observation time was 9.8 months. ]

9.  Secondary:   Overall Survival   [ Time Frame: Up to the data cut-off date of 10 October 2013; median observation time was 9.8 months. ]

10.  Secondary:   Number of Participants With Treatment-emergent Adverse Events   [ Time Frame: From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. ]

11.  Secondary:   100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant   [ Time Frame: From the date of allogeneic HSCT until the data cut-off date of 10 October 2013; median observation time was 7.4 months. ]

12.  Secondary:   Serum Blinatumomab Concentration at Steady State   [ Time Frame: Samples were taken before treatment start and on Days 3, 8, 10, 15, 22, and 29 after infusion start during Cycles 1 and 2. ]

13.  Secondary:   Serum Cytokine Peak Levels   [ Time Frame: Serum samples were collected on Days 1 and 8 at 2 hours and 6 hours after treatment start, and on Day 2 (24 hours) and Day 3 (48 hours) of each treatment cycle and on Days 9 and 10 after dose step. ]

14.  Secondary:   Percentage of Participants With a Best Response of Blast Free Hypoplastic or Aplastic Bone Marrow Within 2 Cycles of Treatment   [ Time Frame: Within the first 2 cycles of treatment, 12 weeks ]

15.  Secondary:   Best Response During the Core Study   [ Time Frame: From the first dose of blinatumomab until 30 days after the end of the last infusion during the core study, or until the data cut-off date of 10 October 2013; a maximum of 7.5 months. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01466179     History of Changes
Other Study ID Numbers: MT103-211
2011-002257-61 ( EudraCT Number )
Study First Received: October 28, 2011
Results First Received: December 21, 2014
Last Updated: July 12, 2016
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency