Clinical Trial Results:
A Pilot, Exploratory, Randomized, Phase 2 Safety Study Evaluating Tumor Cell (Plasma Cell) Mobilization and Apheresis Product Contamination in Plerixafor Plus Non-Pegylated Granulocyte Colony-Stimulating Factor (G-CSF) Mobilized Patients and in Non-Pegylated G-CSF Alone Mobilized Patients
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Summary
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EudraCT number |
2011-004783-30 |
Trial protocol |
BE LT SE EE |
Global end of trial date |
28 Sep 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Oct 2017
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First version publication date |
14 Oct 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ARD12858-MOZ23510
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01753453 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Sanofi Genzyme Corporation
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Sponsor organisation address |
500 Kendall Street , Cambridge, MA, United States, 02142
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Oct 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Sep 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate tumor cell mobilization (TCM) with non-pegylated granulocyte colony-stimulating factor (G-CSF) alone compared with non-pegylated G-CSF plus plerixafor in subjects with multiple myeloma (MM) who are potentially poor mobilizers of hematopoietic stem cells (HSC).
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency.
Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jun 2013
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 8
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Country: Number of subjects enrolled |
Estonia: 5
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Country: Number of subjects enrolled |
Lithuania: 7
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
13
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 5 centres in 3 countries. A total of 28 subjects were screened between 4 June 2013 and 28 September 2016, of whom 20 subjects were randomized in the study. | |||||||||||||||
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Pre-assignment
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Screening details |
Subjects were randomized in 1:1 ratio to receive either G-CSF alone or G-CSF plus plerixafor. | |||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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G-CSF Alone | |||||||||||||||
Arm description |
G-CSF (non-pegylated only) 10 mcg/kg once daily (qd) in the morning for 5 consecutive days. Morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | |||||||||||||||
Arm type |
Non-Investigational Medicinal Product (IMP) | |||||||||||||||
Investigational medicinal product name |
Non-IMP: Granulocyte Colony-Stimulating Factor (G-CSF)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The dose of G-CSF was based on the subject’s actual body weight and G-CSF was administered approximately 1 hour prior to apheresis.
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Arm title
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G-CSF + Plerixafor | |||||||||||||||
Arm description |
G-CSF (non-pegylated only) 10 mcg/kg qd in the morning for 4 consecutive days, Plerixafor 240 mcg/kg in the evening of Day 4, and G-CSF (non-pegylated only) 10 mcg/kg in the morning on Day 5. Evening doses of plerixafor and morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Non IMP: Granulocyte Colony-Stimulating Factor (G-CSF)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The dose of G-CSF was based on the subject’s actual body weight and G-CSF was administered approximately 1 hour prior to apheresis.
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Investigational medicinal product name |
Plerixafor
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Investigational medicinal product code |
AMD3100
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Other name |
Mozobil®
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Plerixafor 240 mcg/kg was administered 10 to 11 hours prior to the initiation of apheresis.
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Baseline characteristics reporting groups
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Reporting group title |
G-CSF Alone
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Reporting group description |
G-CSF (non-pegylated only) 10 mcg/kg once daily (qd) in the morning for 5 consecutive days. Morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
G-CSF + Plerixafor
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Reporting group description |
G-CSF (non-pegylated only) 10 mcg/kg qd in the morning for 4 consecutive days, Plerixafor 240 mcg/kg in the evening of Day 4, and G-CSF (non-pegylated only) 10 mcg/kg in the morning on Day 5. Evening doses of plerixafor and morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
G-CSF Alone
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Reporting group description |
G-CSF (non-pegylated only) 10 mcg/kg once daily (qd) in the morning for 5 consecutive days. Morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | ||
Reporting group title |
G-CSF + Plerixafor
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Reporting group description |
G-CSF (non-pegylated only) 10 mcg/kg qd in the morning for 4 consecutive days, Plerixafor 240 mcg/kg in the evening of Day 4, and G-CSF (non-pegylated only) 10 mcg/kg in the morning on Day 5. Evening doses of plerixafor and morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | ||
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End point title |
Percentage of Myeloma Tumor Cells/CD34+ Cell Count in Peripheral Blood [1] | ||||||||||||
End point description |
The presence of myeloma tumor cells in peripheral blood was detected by flow cytometry analysis. Overall data from Day 5 pre-G-CSF administration up to Day 8 pre-G-CSF administration was calculated as sum of total myeloma tumors cells count/total CD34+ cells count from Day 5 up to Day 8. Analysis was performed on ITT population defined as all randomized population analyzed according to the treatment group allocated by randomization regardless of whether subjects received any study drug or received a different study drug from which they were randomized.
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End point type |
Primary
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End point timeframe |
Day 5 up to Day 8
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| 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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Myeloma Tumor Cells/CD34+ Cells Count Per Cumulative G-CSF Dose (mcg/kg) in Peripheral Blood [2] | ||||||||||||
End point description |
The presence of myeloma tumor cells in peripheral blood was detected by flow cytometry analysis. Overall data from Day 5 pre-G-CSF administration up to Day 8 pre-G-CSF administration was calculated as: (total cumulative myeloma tumors cells count/total cumulative CD34+ cells count) divided by (cumulative G-CSF dose since Day 1/Body weight in kg), where G-CSF cumulative dose was the sum of all doses of G-CSF from the 1st administration to the last dose received prior the peripheral blood sample analyzed. The value of the body weight was the last available value before the start of first planned G-CSF. Analysis was performed on ITT population.
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End point type |
Primary
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End point timeframe |
Day 5 up to Day 8
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| Notes [2] - 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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Myeloma Tumor Cells/CD34+ Cells Count per Cumulative Plerixafor Dose (mcg/kg) in Peripheral Blood [3] [4] | ||||||||
End point description |
The presence of myeloma tumor cells in peripheral blood was detected by flow cytometry analysis. Overall data from Day 5 pre-G-CSF administration up to Day 8 pre-G-CSF administration was calculated as: (total cumulative myeloma tumors cells count/total cumulative CD34+ cells count) divided by (cumulative Plerixafor dose since Day 4/Body weight in kg), where plerixafor cumulative dose was the sum of all doses of plerixafor from the 1st administration of plerixafor (Day 4) to the last dose of plerixafor received prior the peripheral blood sample analyzed. The value of the body weight was the last available value before the start of first planned G-CSF. Analysis was performed on ITT population.
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End point type |
Primary
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End point timeframe |
Day 5 up to Day 8
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| Notes [3] - 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: As the endpoint is descriptive in nature, no statistical analysis is provided. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The end point is reporting results only for the arm in which Plerixafor was administered. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Day 4 in Tumor Cell Mobilization (TCM) in Peripheral Blood at Day 5 [5] | ||||||||||||
End point description |
The Change in TCM was calculated as: TCM value at Day 5 (pre-G-CSF administration) minus TCM value at Day 4 (pre-G-CSF administration). Analysis was performed on ITT population. Number of subjects analyzed=subjects with available data for this endpoint.
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End point type |
Primary
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End point timeframe |
Day 4, Day 5
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| Notes [5] - 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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Myeloma Tumor Cells (*10^5 Cells/Kg) in the Apheresis Product [6] | ||||||||||||
End point description |
The overall number of myeloma tumor cells was calculated as: sum of total myeloma tumor cells in apheresis product from Day 5 up to Day 8. Analysis was performed on ITT population.
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End point type |
Primary
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End point timeframe |
Day 5 up to Day 8
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| Notes [6] - 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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Mobilizing At least 4.5*10^5 Myeloma Tumor cells/kg Body Weight in Apheresis Product [7] | ||||||||||||
End point description |
The percentage of subjects mobilizing at least 4.5*10^5 myeloma tumor cells/kg body weight in the apheresis product from Day 5 up to Day 8 were reported. Overall data was calculated as subjects with the sum of total myeloma tumor cells with >=4.5*10^5 myeloma tumor cells/kg in apheresis product from Day 5 up to Day 8. Analysis was performed on ITT population.
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End point type |
Primary
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End point timeframe |
Day 5 up to Day 8
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| Notes [7] - 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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Total CD34+ (*10^6 cells/kg) Stem Cell Yield | ||||||||||||
End point description |
Total CD34+ (*10^6 cells/kg) stem cell yield from apheresis 1 up to apheresis 4 (up to Day 8) were reported. Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Day 5 up to Day 8
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Reaching the Minimal Target of >=2*10^6 CD34+ cells/kg | ||||||||||||
End point description |
Percentage of subjects reaching the minimal target of >=2*10^6 CD34+ cells/kg from Day 5 up to Day 8 were reported. Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Day 5 up to Day 8
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Reaching the Optimal Target of >=6*10^6 CD34+ cells/kg | ||||||||||||
End point description |
Percentage of subjects reaching the optimal target of >=6*10^6 CD34+ cells/kg from Day 5 up to Day 8 were reported. Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Day 5 up to Day 8
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects That Proceeded to Transplantations | ||||||||||||
End point description |
Transplantation of the collected apheresis product was performed within 2 months of last apheresis according to the standard procedures at the site. Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Up to two months after last apheresis (last apheresis = up to Day 8)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall survival | ||||||||||||
End point description |
Overall survival was defined as the time interval between the date of randomization and the date of death from any cause. In the absence of death before the cut-off date for the final analysis, overall survival time was censored at the earlier between the last date subject was known to be alive and the cut-off date. Estimation was performed by Kaplan-Meier method. Analysis was performed on ITT population. 99999 represented that data was not estimable due to the low number of subjects who died.
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End point type |
Secondary
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End point timeframe |
Baseline until death or study cut-off (up to 2 years follow up)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Best Overall Response (BOR) | ||||||||||||||||||||||||||||||
End point description |
BOR was assessed using International Myeloma Working Group Uniform Response Criteria. Complete Response(CR):Negative immunofixation on serum & urine & disappearance of any soft tissue plasmacytomas & <5% plasma cells in bone marrow.Stringent CR(sCR):CR + normal free light chain(FLC)ratio & absence of clonal cells in bone marrow by immunohistochemistry/immunofluorescence.Very good partial response(VGPR):Serum & urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-component + urine M-component level <100 mg/24 hr.Partial Response(PR):>=50% reduction of serum M-protein and reduction in 24 hrs urinary M-protein by >=90% or to <200 mg/24Hr.Stable disease: Not meeting criteria for CR,VGPR,PR/Progressive Disease (PD).PD:Increase of >25% from lowest response value in any one or more of the following: •Serum M-component and/or (absolute increase must be >=0.5 g/dL)•Urine M-component and/or(absolute increase must be >=200mg/24 hr).ITT population.
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End point type |
Secondary
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End point timeframe |
From randomization until disease progression (DP) or the end of the 2 years follow-up
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (up to follow up visit of 2 year) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported AEs and deaths are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (any AEs occurring from the first G-CSF administration up to end of the 2-year follow-up period).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
G-CSF Alone
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Reporting group description |
G-CSF (non-pegylated only) 10 mcg/kg once daily (qd) in the morning for 5 consecutive days. Morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
G-CSF + Plerixafor
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Reporting group description |
G-CSF (non-pegylated only) 10 mcg/kg/day qd in the morning for 4 consecutive days, Plerixafor 240 mcg/kg in the evening of Day 4, and G-CSF (non-pegylated only) 10 mcg/kg in the morning on Day 5. Evening doses of plerixafor and morning doses of G-CSF was followed by apheresis and continued for up to a maximum of 4 apheresis or until >=6*10^6 CD34+ cells/kg were collected. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
