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: January 20, 2015
Last verified: January 2015
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  
Number of Participants  
[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  
Disease stage entry criteria met [2]
[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  
Number of prior relapses  
[units: participants]
 
0     16  
1     107  
2     46  
>2     20  
Prior allogeneic HSCT and prior relapses [3]
[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  
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 [4]
[units: months]
Median (Full Range)
  1.38    (0.1 to 56.8)  
Baseline bone marrow blast category [5]
[units: participants]
 
< 10%     1  
10% - < 50%     43  
≥ 50%     145  
[1] Race was not permitted to be collected in France
[2] HSCT = hematopoietic stem cell transplantation
[3] alloHSCT = allogeneic hematopoietic stem cell transplantation
[4] Reported for 173 participants with a prior relapse (the other16 participants were primary refractory with no prior relapses).
[5] 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


No publications provided by Amgen Research (Munich) GmbH

Publications automatically indexed to this study:

Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01466179     History of Changes
Other Study ID Numbers: MT103-211, 2011-002257-61
Study First Received: October 28, 2011
Results First Received: December 21, 2014
Last Updated: January 20, 2015
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