Clinical Trial Results:
Phase 2, Safety and Efficacy Study of Isatuximab, an Anti-CD38 Monoclonal Antibody, Administered by Intravenous (IV) Infusion in Patients with Relapsed or Refractory T-acute Lymphoblastic Leukemia (T-ALL) or T-lymphoblastic Lymphoma (T-LBL)
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Summary
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EudraCT number |
2016-002739-14 |
Trial protocol |
LT HU FI IT |
Global end of trial date |
14 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Nov 2018
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First version publication date |
22 Nov 2018
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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 |
ACT14596
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02999633 | ||
WHO universal trial number (UTN) |
U1111-1179-5294 | ||
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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,
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Public contact |
Sanofi aventis recherche & développement, Trial Transparency Team, US@sanofi.com
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Scientific contact |
Sanofi aventis recherche & développement, Trial Transparency Team, 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 |
05 Feb 2018
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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 |
14 Nov 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of isatuximab in subjects with relapsed or refractory T-ALL or T-LBL as measured by overall response rate (ORR) (as per National Comprehensive Cancer Network [NCCN] guidelines).
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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 |
14 Mar 2017
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Long term follow-up planned |
No
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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 |
Finland: 1
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Country: Number of subjects enrolled |
France: 6
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Country: Number of subjects enrolled |
Lithuania: 1
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Russian Federation: 3
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
14
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EEA total number of subjects |
10
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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) |
1
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Adults (18-64 years) |
10
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in 6 countries. A total of 16 subjects were screened of those 2 subjects failed screening: 1 subject for evidence of ongoing infection and 1 subject for not meeting the criterion for relapsed or refractory T-acute lymphoblastic leukemia (ALL)/T-lymphoblastic lymphoma (LBL). | ||||||||||||
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Pre-assignment
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Screening details |
The first subject was enrolled on 14 March 2017. A total of 14 subjects were enrolled to receive isatuximab. The study was early terminated on 08 Nov 2017. | ||||||||||||
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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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Isatuximab | ||||||||||||
Arm description |
Subjects received intravenous administration of isatuximab at a dose of 20 mg/kg at Day 1, 8, 15 and 22 of each Cycle (up to 2 treatment cycles, each cycle 28 days). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Isatuximab
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Investigational medicinal product code |
SAR650984
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received intravenous administration of isatuximab at a dose of 20 milligram/kilogram (mg/kg).
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Baseline characteristics reporting groups
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Reporting group title |
Isatuximab
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Reporting group description |
Subjects received intravenous administration of isatuximab at a dose of 20 mg/kg at Day 1, 8, 15 and 22 of each Cycle (up to 2 treatment cycles, each cycle 28 days). | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Isatuximab
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Reporting group description |
Subjects received intravenous administration of isatuximab at a dose of 20 mg/kg at Day 1, 8, 15 and 22 of each Cycle (up to 2 treatment cycles, each cycle 28 days). | ||
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End point title |
Percentage of Subjects With Objective Response [1] | ||||||||
End point description |
Objective response was defined as percentage of subjects with complete response or with complete response with incomplete peripheral recovery as per National Comprehensive Cancer Network (NCCN) guidelines. Complete response was defined as no circulating blasts or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement, trilineage hematopoiesis and less than 5 percentage blasts, absolute neutrophil count (ANC) greater than 1000 per micro liter, platelets less than 100 000 per micro liter, no recurrence for 4 weeks. Complete response with incomplete blood count recovery (Cri) meet all criteria for complete response except platelet count and/or ANC. Safety analysis set included all subjects who received at least 1 dose of isatuximab.
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End point type |
Primary
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End point timeframe |
Baseline until disease progression or death (maximum duration: 12.1 weeks)
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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: Only descriptive data was planned to be analysed for this study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) | ||||||||
End point description |
DOR defined as time (in days) from date of first response until date of first documented progressive disease (PD) or death (from any cause), whichever came first. Progressive disease as per NCCN guidelines was defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. The endpoint was not analyzed due to lack of objective response. There was no specific additional data collected for the analysis of DOR as this endpoint was to be derived using time point responses and death information that were collected and analyzed as part of primary endpoint and safety endpoints, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline until disease progression or death (maximum duration: 12.1 weeks)
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| Notes [2] - The endpoint was not analyzed due to lack of objective response. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival (PFS) | ||||||||
End point description |
PFS was defined as the time interval (in days) from the date of first study drug administration to the date of first observation of PD or death due to any cause, whichever came first. PD as per NCCN guidelines was defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. The endpoint was not analyzed due to lack of objective response. There was no specific additional data collected for the analysis of PFS as this endpoint was to be derived using time point responses and death information that were collected and analyzed as part of primary endpoint and safety endpoints, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline until disease progression or death (maximum duration: 12.1 weeks)
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| Notes [3] - The endpoint was not analyzed due to lack of objective response. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival | ||||||||
End point description |
OS was defined as the time interval from the date of first study drug administration to the date of death due to any cause. The endpoint was not analyzed due to lack of objective response. There was no specific additional data collected for the analysis of OS as this endpoint was to be derived using time point responses and death information that were collected and analyzed as part of primary endpoint and safety endpoints, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline until disease progression or death (maximum duration: 12.1 weeks)
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| Notes [4] - The endpoint was not analyzed due to lack of objective response. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects With Minimal Residual Disease (MRD) | ||||||
End point description |
Presence of MRD was measured by sequencing and/or flow cytometry in subjects achieving CR and CRi. Complete response was defined as no circulating blasts or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement, trilineage hematopoiesis and less than 5 percentage blasts, absolute neutrophil count (ANC) greater than 1000 per micro liter, platelets less than 100 000 per micro liter, no recurrence for 4 weeks. Complete response with incomplete blood count recovery (Cri) meet all criteria for complete response except platelet count and/or ANC. The endpoint was not analyzed because no subject achieved CR or CRi.
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End point type |
Secondary
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End point timeframe |
Baseline until disease progression or death (maximum duration: 12.1 weeks)
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| Notes [5] - The endpoint was not analyzed because no subject achieved CR or CRi. |
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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 |
Baseline up to 30 days after last dose of study drug administration (up to maximum of 12.1 weeks)
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Adverse event reporting additional description |
Reported Adverse events(AEs) are treatment emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (from first study treatment administration until 30 days after the last administration of study treatment). Safety analysis set included all subjects who received at least 1 dose of isatuximab.
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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 |
20.1
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Reporting groups
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Reporting group title |
Isatuximab
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Reporting group description |
Subjects received intravenous administration of isatuximab at a dose of 20 mg/kg at Day 1, 8, 15 and 22 of each Cycle (up to 2 treatment cycles, each cycle 28 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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27 Feb 2017 |
Following amendments were made:
- Change contraception period from ‘2 weeks prior to screening’ into ‘2 weeks prior to the first dose of isatuximab
- Added blood typing and screen at screening
- Removed mandatory chest X-ray from study time points other than screening period
- Clarified the definition of Pharmacokinetic (PK) population
- Clarified PK/PDy sampling time window and allowances
- Reduced the number of PK samplings during the study
- Added immunophenotyping sample collection during the induction period
- Clarified the bone marrow sample collections and change sampling timing for receptor occupancy/receptor density
- Editorial changes to improve clarity (add study name, abbreviations, grammatical corrections
- Update of bioanalysis methods and locations for cytokines and markers of activated
complements panel
- Add interleukin (IL)-4 to the cytokine panel. |
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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. | |||
| The study was stopped prior to the interim analysis due to lack of efficacy of isatuximab monotherapy for this study population. Therefore, majority of efficacy evaluations originally planned were no longer considered relevant and were not performed. | |||
