Clinical Trial Results:
An Open Label, Multicenter, Phase II Study of Intravenous SAR3419, an Anti-CD19 Antibody-Maytansine Conjugate, in Combination with Rituximab in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphomas
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Summary
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EudraCT number |
2011-002865-39 |
Trial protocol |
SE DE AT |
Global end of trial date |
22 Sep 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Mar 2016
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First version publication date |
20 Mar 2016
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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 |
TCD12333
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01470456 | ||
WHO universal trial number (UTN) |
U1111-1120-0315 | ||
Other trial identifiers |
Study name : SARIT | ||
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Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly, Mazarin, France, 91380
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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 |
16 Oct 2014
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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 |
22 Sep 2014
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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 the objective response rate (ORR) of SAR3419 in combination with rituximab.
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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 |
22 Nov 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
24 Months | ||
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 |
Norway: 1
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Country: Number of subjects enrolled |
France: 51
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Worldwide total number of subjects |
52
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EEA total number of subjects |
52
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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) |
21
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From 65 to 84 years |
30
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85 years and over |
1
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Recruitment
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Recruitment details |
The study was conducted at 12 sites in France and Norway. A total of 85 subjects were screened between 22 November 2011 and 21 February 2013. | ||||||||||
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Pre-assignment
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Screening details |
Of 85 screened subjects, 32 were screen failure; the screen failures were due to failure to meet the inclusion/exclusion criteria. Of 53 included subjects, 1 was not treated due to disease progression. | ||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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SAR3419 + Rituximab | ||||||||||
Arm description |
SAR3419 and Rituximab administered weekly from Weeks 1 to 4, then biweekly on Weeks 6, 8, 10, and 12. One cycle was defined as a 4-week period, except Cycle 1, which was to last 5 weeks (4 weekly administrations followed by a week's rest). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
SAR3419
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
SAR3419 55 mg/m² infusion, administered over approximately an hour.
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Investigational medicinal product name |
Rituximab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Rituximab 375 mg/m² administered over approximately 4 hours.
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Baseline characteristics reporting groups
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Reporting group title |
SAR3419 + Rituximab
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Reporting group description |
SAR3419 and Rituximab administered weekly from Weeks 1 to 4, then biweekly on Weeks 6, 8, 10, and 12. One cycle was defined as a 4-week period, except Cycle 1, which was to last 5 weeks (4 weekly administrations followed by a week's rest). | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SAR3419 + Rituximab
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Reporting group description |
SAR3419 and Rituximab administered weekly from Weeks 1 to 4, then biweekly on Weeks 6, 8, 10, and 12. One cycle was defined as a 4-week period, except Cycle 1, which was to last 5 weeks (4 weekly administrations followed by a week's rest). | ||
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End point title |
Objective Response Rate (ORR) [1] | ||||||||
End point description |
ORR was defined as the percentage of subjects achieving a complete response (CR) or partial response (PR), assessed based on International Workshop Guidelines (IWG) Cheson 2007 criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. Analysis was performed on per protocol (PP) population including all treated subjects who had an evaluable response assessment during treatment or end of treatment visit and without any important protocol deviation impacting efficacy.
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End point type |
Primary
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End point timeframe |
Baseline; end of the treatment and then every 3 months during the follow-up until progression or initiation of further anticancer therapy (24 months)
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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: The data is provided as a separate attachment. |
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Attachments |
Statistical Analyses for ORR |
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| Notes [2] - 45 out of 52 subjects were eligible for the PP population. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response | ||||||||||
End point description |
Duration of response was defined as the time interval from the date of first occurrence of complete response or partial response to the date of first documentation of disease progression (DP) or death due to any cause, which ever occurred first. Responses were assessed based on IWG Cheson 2007 criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. DP was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. Duration of response was calculated using the Kaplan-Meier method. Number of subjects with duration of response ≤6 months and >6 months are provided. Analysis was performed on PP population.
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End point type |
Secondary
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End point timeframe |
Baseline; end of the treatment and then every 3 months during the follow-up until progression or initiation of further anticancer therapy (24 months)
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| Notes [3] - 45 out of 52 subjects were eligible for the PP population. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Progression Free Survival | ||||||||
End point description |
Progression-free survival was defined as the time interval (in months) from the date of first study treatment infusion to the date of first occurrence of progression or death from any cause, whichever occurred first. DP was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. Duration of response was calculated using the Kaplan Meier method. Analysis was performed on PP population.
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End point type |
Secondary
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End point timeframe |
From the date of first study treatment infusion to the date of first occurrence of progression or death from any cause (24 months)
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| Notes [4] - 45 out of 52 subjects were eligible for the PP population. |
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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 (in months) from the date of first study treatment infusion to the date of death from any cause. Analysis was performed on safety population included all treated subjects.
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End point type |
Secondary
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End point timeframe |
From the date of first study treatment infusion to the date of death from any cause (24 months)
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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 (AE) were collected from signature of the informed consent form up to the final visit (Month 24) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported adverse events and death are treatment-emergent that is AEs that developed/worsened and death that occurred during the ‘on treatment period’ (from first study treatment infusion to 42 days after last study treatment infusion [i.e, last infusion of last cycle]).
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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 |
17.0
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Reporting groups
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Reporting group title |
SAR3419 + Rituximab
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Reporting group description |
SAR3419 and Rituximab administered weekly from Weeks 1 to 4, then biweekly, on Weeks 6, 8, 10, and 12. One cycle was defined as a 4-week period, except Cycle 1, which was to last 5 weeks (4 weekly administrations followed by a week's rest). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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22 Sep 2011 |
- Pregnancy tests which were initially required at baseline and end of treatment Visit were performed at Day 1 of each cycle.
- Contraception which was required to be continued during 3 months after the last treatment administration was extended until 12 months after the last treatment administration.
- To provide the study name.
- To correct the formulation and instruction for preparing and administrating the investigational medicinal product in the clinical trial summary and protocol. |
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16 Dec 2011 |
- To correct the schedule for tumor assessment in reference to response criteria Cheson 2007 applying to diffuse large B-cell lymphoma (DLBCL) being a fluorodeoxyglucose-avid (FDG-avid), aggressive lymphoma. Both computed tomography (CT) and positron emission tomography (PET) scans were performed for any subject at baseline and at the end of treatment Visit (42 days after the last treatment administration). For non-progressing subjects at the end of treatment, surveillance CT scans were performed 3 months during the follow-up period.
- To remove the central reviews for both histology confirmation and disease response in this phase II Proof of Concept study.
- To add the option of retrospectively using archived diagnostic biopsies in case of missing material for exploratory endpoint at study entry.
- To answer the exploratory endpoint of the study, all subjects must had either a recent biopsy or a free needle aspiration (FNA) at study entry. Any effort should be done in order to obtain fresh biopsies. At the end of the study, the diagnosis biopsy might be retrospectively collected and used for the centralized analysis of the selected biomarkers defined in Hans and Choi algorithms. If necessary, a specific informed consent was to be obtained.
- To revise the reporting of biological results in the safety follow-up period after further anticancer therapy was administered.
- To add the pharmacokinetic (PK) parameters as an endpoint of the interim analysis on the first 20 subjects.
- To clarify the stopping rules and timing of the interim analysis.
- To harmonize the safety follow-up period as a 42-day period. |
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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 | |||
