Back to resultsTemsirolimus in Recurrent Primary Central Nervous System (CNS) Lymphoma
Primary Purpose
Recurrent or Refractory Primary CNS Lymphoma
Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
temsirolimus
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent or Refractory Primary CNS Lymphoma focused on measuring temsirolimus, primary CNS lymphoma, PCNSL, salvage treatment
Eligibility Criteria
Inclusion Criteria:
- Primary CNS lymphoma diagnosed histologically or by cerebrospinal fluid cytology; absence of systemic lymphoma manifestations
- Relapse or lymphoma progression after/during high-dose methotrexate containing first-line chemotherapy or alternative therapy in the case of contraindications against high-dose methotrexate
- ECOG performance score ≤ 2
- Age ≥18 years and ≤ 75 years
- Life expectancy of at least 3 months
- Absence of active infection
- Negative HIV serology
- Adequate renal function (GFR >30ml/h)
- Adequate bone marrow reserve (neutrophils > 1500/µl, platelets > 80,000/µl)
- Bilirubin <1.5x upper limit of normal (ULN), ALT and AST <3x ULN
- At least 3 weeks interval from prior cytostatic treatment
- Negative pregnancy test
- Patient accessible for treatment and follow-up
- Patient compliance
- Signed informed consent
Exclusion Criteria:
- Secondary CNS lymphoma
- Primary intraocular lymphoma
- Patient eligible for high-dose chemotherapy and autologous stem-cell transplantation
- Concurrent treatment within another clinical trial
- Concurrent other malignant disease
- Symptomatic congestive heart failure (≥NYHA II)
- Active or uncontrolled chronic infection
- Severe concomitant disease incompatible with study conduct
- History of cerebral bleeding
- Concomitant treatment with strong CYP3A4/5-inductors or -inhibitors
- Premenopausal women without highly effective contraception (defined as Pearl index <1)
- Pregnant or lactating women
- Refusal to record and pass on pseudonymized disease and treatment related data as part of the treatment protocol
- Concurrent admission to a psychiatric institution by public order
Sites / Locations
- Charité Campus Benjamin FranklinRecruiting
- Neurology, Knappschaftskrankenhaus Bochum, Bochum UniversityRecruiting
- Neurology, University Hospital BonnRecruiting
- Hematology, Klinikum Frankfurt/Oder
- Hematology, University Hospital Heidelberg
- Klinikum Grosshadern, University Hospital MunichRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Temsirolimus
Arm Description
Weekly IV temsirolimus
Outcomes
Primary Outcome Measures
Overall response rate
Secondary Outcome Measures
Safety
Time to progression of disease
Penetration of temsirolimus into cerebrospinal fluid
Full Information
NCT ID
NCT00942747
First Posted
July 20, 2009
Last Updated
April 15, 2013
Sponsor
Charite University, Berlin, Germany
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00942747
Brief Title
Temsirolimus in Recurrent Primary Central Nervous System (CNS) Lymphoma
Official Title
Phase 2 Study of Temsirolimus in Refractory and Recurrent Primary CNS Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Unknown status
Study Start Date
July 2009 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
June 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open-label trial investigating the efficacy of temsirolimus in recurrent or refractory primary CNS lymphoma (PCNSL) after initial chemotherapy with a high-dose methotrexate containing regimen. 37 patients are planned to be treated with weekly infusions of 25mg Temsirolimus (first 3 patients) or 75mg Temsirolimus (all other patients) up to a maximum of 12 months. The trial is designed in two stages, if less than one of the first 12 patients responds to treatment, the trial is stopped. In addition to efficacy, safety and penetration of temsirolimus into the cerebrospinal fluid will be investigated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent or Refractory Primary CNS Lymphoma
Keywords
temsirolimus, primary CNS lymphoma, PCNSL, salvage treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Temsirolimus
Arm Type
Experimental
Arm Description
Weekly IV temsirolimus
Intervention Type
Drug
Intervention Name(s)
temsirolimus
Other Intervention Name(s)
Torisel, CCI-770
Intervention Description
Weekly infusion of 25mg Temsirolimus (first 3 patients) or 75mg Temsirolimus (all other patients) up to a maximum of 12 months in the case of continuing response to treatment
Primary Outcome Measure Information:
Title
Overall response rate
Time Frame
Weeks 4, 12, every 12 weeks thereafter
Secondary Outcome Measure Information:
Title
Safety
Time Frame
continuous
Title
Time to progression of disease
Time Frame
Weeks 4, 12, every 12 weeks thereafter or upon clinical suspicion of disease progression
Title
Penetration of temsirolimus into cerebrospinal fluid
Time Frame
Weeks 1, 4 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Primary CNS lymphoma diagnosed histologically or by cerebrospinal fluid cytology; absence of systemic lymphoma manifestations
Relapse or lymphoma progression after/during high-dose methotrexate containing first-line chemotherapy or alternative therapy in the case of contraindications against high-dose methotrexate
ECOG performance score ≤ 2
Age ≥18 years and ≤ 75 years
Life expectancy of at least 3 months
Absence of active infection
Negative HIV serology
Adequate renal function (GFR >30ml/h)
Adequate bone marrow reserve (neutrophils > 1500/µl, platelets > 80,000/µl)
Bilirubin <1.5x upper limit of normal (ULN), ALT and AST <3x ULN
At least 3 weeks interval from prior cytostatic treatment
Negative pregnancy test
Patient accessible for treatment and follow-up
Patient compliance
Signed informed consent
Exclusion Criteria:
Secondary CNS lymphoma
Primary intraocular lymphoma
Patient eligible for high-dose chemotherapy and autologous stem-cell transplantation
Concurrent treatment within another clinical trial
Concurrent other malignant disease
Symptomatic congestive heart failure (≥NYHA II)
Active or uncontrolled chronic infection
Severe concomitant disease incompatible with study conduct
History of cerebral bleeding
Concomitant treatment with strong CYP3A4/5-inductors or -inhibitors
Premenopausal women without highly effective contraception (defined as Pearl index <1)
Pregnant or lactating women
Refusal to record and pass on pseudonymized disease and treatment related data as part of the treatment protocol
Concurrent admission to a psychiatric institution by public order
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Agnieszka Korfel, MD
Phone
+49308445
Ext
4096
Email
agnieszka.korfel@charite.de
First Name & Middle Initial & Last Name or Official Title & Degree
Philipp Kiewe, MD
Phone
+493064499
Ext
5225
Email
philipp.kiewe@charite.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Agnieszka Korfel, MD
Organizational Affiliation
Charite University, Berlin, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité Campus Benjamin Franklin
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Agnieszka Korfel, MD
Phone
+49308445
Ext
4096
Email
agnieszka.korfel@charite.de
First Name & Middle Initial & Last Name & Degree
Philipp Kiewe, MD
Phone
+493064499
Ext
5225
Email
philipp.kiewe@charite.de
First Name & Middle Initial & Last Name & Degree
Philipp Kiewe, MD
First Name & Middle Initial & Last Name & Degree
Agnieszka Korfel, MD
First Name & Middle Initial & Last Name & Degree
Martin Neumann, MD
First Name & Middle Initial & Last Name & Degree
Stephan Kreher, MD
Facility Name
Neurology, Knappschaftskrankenhaus Bochum, Bochum University
City
Bochum
ZIP/Postal Code
44892
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Uwe Schlegel, MD
Phone
+49-2342993701
Email
simone.middelhauve@kk-bochum.de
First Name & Middle Initial & Last Name & Degree
Simone Middelhauve
Phone
+49-2342993701
Email
simone.middelhauve@kk-bochum.de
Facility Name
Neurology, University Hospital Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulrich Herrlinger, MD
Phone
+49-222828719887
Email
christiane.landwehr@ukb.uni-bonn.de
First Name & Middle Initial & Last Name & Degree
Christiane Landwehr
Phone
+49-222828719887
Email
christiane.landwehr@ukb.uni-bonn.de
Facility Name
Hematology, Klinikum Frankfurt/Oder
City
Frankfurt an der Oder
ZIP/Postal Code
15236
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Kiel, MD
Phone
+4933-55484604
Email
melanie.binsker@klinikum-ffo.de
First Name & Middle Initial & Last Name & Degree
Melanie Binsker
Phone
+4933-55484604
Email
melanie.binsker@klinikum-ffo.de
Facility Name
Hematology, University Hospital Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gerlinde Egerer, MD
Phone
+49-6221568029
Email
martina.gronkowski@med.uni-heidelberg.de
First Name & Middle Initial & Last Name & Degree
Martina Gronkowski
Phone
+49-6221568029
Email
martina.gronkowski@med.uni-heidelberg.de
Facility Name
Klinikum Grosshadern, University Hospital Munich
City
Munich
ZIP/Postal Code
81377
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Dreyling, MD
Phone
+498970955202
Email
carmen.carlucci@med.uni-muenchen.de
First Name & Middle Initial & Last Name & Degree
Carmen Carlucci
Phone
+498970955202
Email
carmen.carlucci@med.uni-muenchen.de
12. IPD Sharing Statement
Citations:
PubMed Identifier
18094423
Citation
Kuhn JG, Chang SM, Wen PY, Cloughesy TF, Greenberg H, Schiff D, Conrad C, Fink KL, Robins HI, Mehta M, DeAngelis L, Raizer J, Hess K, Lamborn KR, Dancey J, Prados MD; North American Brain Tumor Consortium and the National Cancer Institute. Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma. Clin Cancer Res. 2007 Dec 15;13(24):7401-6. doi: 10.1158/1078-0432.CCR-07-0781.
Results Reference
background
Citation
Smith SM, Pro B, Cisneros A, Smith S, Stiff P, Lester E, Modi S, Dancey JE, Vokes EE, van Besien E. Activity of single agent temsirolimus (CCI-779) in non-mantle cell non-Hodgkin lymphoma subtypes. J Clin Oncol 2008:26 (May 20 suppl; abstr 8514).
Results Reference
background
PubMed Identifier
19581539
Citation
Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F, Strahs A, Berkenblit A, Hanushevsky O, Clancy J, Hewes B, Moore L, Coiffier B. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009 Aug 10;27(23):3822-9. doi: 10.1200/JCO.2008.20.7977. Epub 2009 Jul 6.
Results Reference
background
PubMed Identifier
18543327
Citation
Ansell SM, Inwards DJ, Rowland KM Jr, Flynn PJ, Morton RF, Moore DF Jr, Kaufmann SH, Ghobrial I, Kurtin PJ, Maurer M, Allmer C, Witzig TE. Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer. 2008 Aug 1;113(3):508-14. doi: 10.1002/cncr.23580.
Results Reference
background
PubMed Identifier
15983389
Citation
Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P, Ansell SM, Luyun R, Flynn PJ, Morton RF, Dakhil SR, Gross H, Kaufmann SH. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol. 2005 Aug 10;23(23):5347-56. doi: 10.1200/JCO.2005.13.466. Epub 2005 Jun 27.
Results Reference
background
PubMed Identifier
17161912
Citation
Costa LJ. Aspects of mTOR biology and the use of mTOR inhibitors in non-Hodgkin's lymphoma. Cancer Treat Rev. 2007 Feb;33(1):78-84. doi: 10.1016/j.ctrv.2006.10.004. Epub 2006 Dec 11.
Results Reference
background
PubMed Identifier
26976424
Citation
Korfel A, Schlegel U, Herrlinger U, Dreyling M, Schmidt C, von Baumgarten L, Pezzutto A, Grobosch T, Kebir S, Thiel E, Martus P, Kiewe P. Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma. J Clin Oncol. 2016 May 20;34(15):1757-63. doi: 10.1200/JCO.2015.64.9897. Epub 2016 Mar 14.
Results Reference
derived
Learn more about this trial
Temsirolimus in Recurrent Primary Central Nervous System (CNS) Lymphoma
We'll reach out to this number within 24 hrs