Clinical Trial Results:
A phase II trial to evaluate the safety, feasibility and efficacy of a salvage therapy consisting of the mTOR inhibitor Temsirolimus (Torisel™) added to the standard therapy of Rituximab and DHAP for the treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma – the STORM trial
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Summary
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EudraCT number |
2011-001491-20 |
Trial protocol |
DE |
Global end of trial date |
01 Nov 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
18 May 2022
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First version publication date |
18 May 2022
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Other versions |
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Summary report(s) |
STORM_Report |
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 |
STORM-2011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01653067 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ruprecht-Karls-University Heidelberg, Medical Faculty
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Sponsor organisation address |
INF , Heidelberg, Germany,
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Public contact |
Julia Meißner, Ruprecht-Karls University Heidelberg, Medical Faculty, 0049 6221568001, julia.meissner@med.uni-heidelberg.de
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Scientific contact |
Julia Meißner, Ruprecht-Karls University Heidelberg, Medical Faculty, 0049 6221568001, julia.meissner@med.uni-heidelberg.de
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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 |
01 Nov 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Oct 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Nov 2018
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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 |
The STORM-trial consists of two parts.
In the part I (dose escalation of Temsirolimus) the primary objective is to establish a maximum tolerated dose of Temsirolimus in combination with Rituximab and DHAP.
In the part II (full target dose) the primary objective is to evaluate the ORR in patients with relapsed DLBCL.
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Protection of trial subjects |
In a phase 1, a dose escalation was performed to establish a maximum tolerated dose of Temsirolimus in combination with Rituximab and DHAP.
Special attention in Part I and Part II of the study was brought to monitoring of adverse events. Frequency of Adverse events was calculated.
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Background therapy |
All cohorts additionally received: Rituximab (375 mg/m² day 2) Dexamethasone 40 mg day 3-6 Cisplatin 100 mg/m² day 3 (Cisplatin could be replaced in the consecutive cycles by carboplatin AUC 5 if the patient experienced kidney toxicity in the previous cycle, i.e. decrease of creatinine clearance to 60 ml/min or lower.) | ||
Evidence for comparator |
There was no comparator in this trial. | ||
Actual start date of recruitment |
31 Jan 2012
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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 |
Germany: 53
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Worldwide total number of subjects |
53
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EEA total number of subjects |
53
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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) |
33
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From 65 to 84 years |
20
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85 years and over |
0
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Recruitment
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Recruitment details |
Eligible patients with histologically proven diagnosis of DLBCL according to the World Health Organization classification and with first or second relapse of DLBCL were screened. After inclusion patients in part I of the trial received 2 to 4 cycles of 25 or 50 mg of Temsirolimus in combination with R-DHAP depending on the cohort were admitted. | |||||||||
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Pre-assignment
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Screening details |
In total, 55 patients were assessed for eligibility. Fifty-three patients were enrolled, 15 patients in part I and 38 in part II of the study. Two patients were excluded from the study: 1 patient was identified as screening failure and another patient withdrew informed consent before start of treatment, respectively. | |||||||||
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Period 1
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Period 1 title |
Treatment (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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Are arms mutually exclusive |
Yes
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Arm title
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Part I 50 mg Temsirolimus | |||||||||
Arm description |
Part I (to examine dose limiting toxicity). Part I was actually a separate period preceeding part II. | |||||||||
Arm type |
examination of dose limiting toxicity | |||||||||
Investigational medicinal product name |
Temsirolimus 50 mg
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Investigational medicinal product code |
L01E G01
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Patients received 2 to 4 cycles of 50 mg of Temsirolimus
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Arm title
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Part I + II 25 mg Temsirolimus | |||||||||
Arm description |
For the Part II proportion of the trial, Temsirolimus at 25mg on day 1 and 8 was determined as recommended dose following part I. Temsirolimus can be safely added to DHAP and Rituximab with promising activity. | |||||||||
Arm type |
target dose (as established in part I) | |||||||||
Investigational medicinal product name |
Temsirolimus 25 mg
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Investigational medicinal product code |
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Other name |
Torisel
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Patients received 2 to 4 cycles of 25 or 50 mg of Temsirolimus in combination with R-DHAP.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part I 50 mg Temsirolimus
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Reporting group description |
Part I (to examine dose limiting toxicity). Part I was actually a separate period preceeding part II. | ||
Reporting group title |
Part I + II 25 mg Temsirolimus
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Reporting group description |
For the Part II proportion of the trial, Temsirolimus at 25mg on day 1 and 8 was determined as recommended dose following part I. Temsirolimus can be safely added to DHAP and Rituximab with promising activity. | ||
Subject analysis set title |
Total participants
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients of phase 1 (25 mg) and 2 (50 mg)
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End point title |
Overall Response Rate (ORR) [1] | |||||||||
End point description |
In the part II (full target dose) the primary objective was the overall response rate in patients with relapsed DLBCL.
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End point type |
Primary
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End point timeframe |
response at end of salvage therapy
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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: No statistical tests have been performed in this single-arm study. |
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| Notes [2] - 1 missing, 1 no overall response at end of follow-up [3] - no overall response n= 13, missing n=2 |
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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 |
Up to 30 days after the last dose of study drug or the start of new antineoplastic therapy within 30 days after STORM termination.
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Adverse event reporting additional description |
All patients reported at least one AE. A total of 1678 AEs were reported (32 per pat.). Thereof, 253 AEs (15%, 42 per pat.) occurred in the group of patients treated with 50 mg Temsirolimus and 1425 AEs (85%, 30 per pat.) occurred in in the group of patients treated with 25 mg Temsirolimus.
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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 |
22.0
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Reporting groups
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Reporting group title |
Total
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Reporting group description |
All patients included in this single-arm study | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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23 May 2017 |
Change of principal investigator. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/34589671 |
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