Clinical Trial Results:
A therapy and pharmacokinetics study of temsirolimus in patients with refractory and recidivated primary CNS lymphoma.
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Summary
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EudraCT number |
2009-011277-33 |
Trial protocol |
DE |
Global end of trial date |
15 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Dec 2022
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First version publication date |
17 Dec 2022
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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 |
PZNSL
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00942747 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Charité - University Hospital of Berlin
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Sponsor organisation address |
Hindenburgdamm 30, Berlin, Germany, 12200
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Public contact |
Agnieszka Korfel, MD, Department of Hematology and Oncology, Charité University Medicine Berlin, +49 30 450 613 260, agnieszka.korfel@charite.de
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Scientific contact |
Agnieszka Korfel, MD, Department of Hematology and Oncology, Charité University Medicine Berlin, +49 30 450 613 260, agnieszka.korfel@charite.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 |
16 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Dec 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 |
The objective of this study is to assess efficacy of Temsirolimus in patients with refractory and recidivated primary CNS lymphoma
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Protection of trial subjects |
Study conduct followed International Conference on Harmonization Guidelines for Good Clinical Practice, including written informed consent and data monitoring. Baseline assessments included physical and neurologic examination, cranial magnetic resonance imaging (spinal on clinical suspicion only), and ophthalmologic and CSF examination. Safety assessments included physical examinations, adverse event monitoring, and laboratory parameter changes before each infusion. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Response assessment was performed after 4 weeks and every 8 weeks thereafter. Additionally, response assessment was recommended at each time point when progression was suspected. After discontinuing therapy, patients completed an end-of-treatment visit 30 days after their last temsirolimus dose. In patients with PR or CR, remission status was evaluated every 3 months.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Sep 2009
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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: 37
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Worldwide total number of subjects |
37
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EEA total number of subjects |
37
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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) |
0
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From 65 to 84 years |
37
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85 years and over |
0
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Recruitment
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Recruitment details |
Between September 2009 and November 2014, 37 patients were enrolled at four German centers . | ||||||
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Pre-assignment
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Screening details |
The vast majority of patients had intermediate- or high-risk disease according to the Memorial Sloan Kettering Cancer Center score. Patients had received a median of one prior therapy comprising HDMTX in all patients and high-dose cytarabine in 11. Two patients were pretreated with WBRT, three patients with HD-ASCT, and four patients with both. | ||||||
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Period 1
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Period 1 title |
Treatment stage (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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Temsirolimus Arm | ||||||
Arm description |
Among the first three patients who were given 25 mg temsirolimus, two had grade 3 toxicity (one patient had diarrhea, thrombocytopenia, and leukopenia with pneumonia; one patient had pneumonia). Thus, an additional three patients were treated with the same dose. In these patients, no grade 3 to 4 toxicity was observed, and there was a PR in one patient. Thus, per protocol, the study was continued with 75 mg temsirolimus once per week. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Temsirolimus
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
In the first stage, patients were treated with temsirolimus 25 mg intravenously once per week with clemastine premedication. In case of Common Toxicity Criteria grades 3 to 4 toxicity, three additional patients were to be treated with the same dose. If no Common Toxicity Criteria grades 3 to 4 toxicity were observed, all following patients were treated with 75 mg once per week.
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Baseline characteristics reporting groups
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Reporting group title |
Temsirolimus Arm
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Reporting group description |
Among the first three patients who were given 25 mg temsirolimus, two had grade 3 toxicity (one patient had diarrhea, thrombocytopenia, and leukopenia with pneumonia; one patient had pneumonia). Thus, an additional three patients were treated with the same dose. In these patients, no grade 3 to 4 toxicity was observed, and there was a PR in one patient. Thus, per protocol, the study was continued with 75 mg temsirolimus once per week. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Temsirolimus Arm
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Reporting group description |
Among the first three patients who were given 25 mg temsirolimus, two had grade 3 toxicity (one patient had diarrhea, thrombocytopenia, and leukopenia with pneumonia; one patient had pneumonia). Thus, an additional three patients were treated with the same dose. In these patients, no grade 3 to 4 toxicity was observed, and there was a PR in one patient. Thus, per protocol, the study was continued with 75 mg temsirolimus once per week. | ||
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End point title |
Patients responding rate to treatment [1] | ||||||||||||||||||
End point description |
Response assessment was performed after 4 weeks and every 8 weeks thereafter. Additionally, response assessment was recommended at each time point when
progression was suspected. After discontinuing therapy, patients completed an end-of-treatment visit 30 days after their last temsirolimus dose. In patients with PR or CR, remission status was evaluated every 3 months. Survival data were collected every 3 months for up to 2 years from start of study treatment or until study closure.
CR, complete response;
uCR, unconfirmed CR;
PD, progressive disease;
PR, partial remission;
Overall response rate (ORR) of 54% (95% CI, 37% to 71%)
SD; stable disease
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End point type |
Primary
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End point timeframe |
48 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: This was a phase II a two stage design using single-agent temsirolimus in patients. The second stage of the trial was planned to enroll 25 additional patients. After termination of this study stage, the therapy was considered ineffective if fewer than four patients responded. Since there was only one arm and one stage, comparison between groups was not possible. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
CSF Penetration of Temsirolimus | ||||||||||||
End point description |
Fourteen blood/CSF pairs were collected in nine patients:
10 pairs in five patients in the 25-mg cohort and four pairs in four
patients in the 75-mg cohort.
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End point type |
Secondary
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End point timeframe |
48months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression Free survival | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
48 months
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Attachments |
PFS Fig 2(A) |
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End point title |
Overall survival | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
60months
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Attachments |
OS Fig.2 (B) |
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End point title |
Toxicity All Grades | ||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
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 |
2 years
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
3.0
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Reporting groups
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Reporting group title |
Temsirolimus Arm
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Reporting group description |
Temsirolimus Arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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09 Nov 2011 |
new protocol version 2.1 : adjustment of schedule and dosage, the process organization to the termination criteria |
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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. | |||
| limitation was the preferential inclusion of elderly patients whose initial treatment is frequently not according to the current standards used in younger patients. Generalization of our results should thus be viewed. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/26976424 |
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