Clinical trial NCT00942747: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Recurrent or Refractory Primary CNS Lymphoma
Keywords: temsirolimus, primary CNS lymphoma, PCNSL, salvage treatment
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2009-07-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall response rate
timeFrame: Weeks 4, 12, every 12 weeks thereafter
Secondary outcomes:
measure: Safety
timeFrame: continuous
measure: Time to progression of disease
timeFrame: Weeks 4, 12, every 12 weeks thereafter or upon clinical suspicion of disease progression
measure: Penetration of temsirolimus into cerebrospinal fluid
timeFrame: Weeks 1, 4 and 12
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
city: Bochum
country: Germany
facility: Neurology, Knappschaftskrankenhaus Bochum, Bochum University
city: Bonn
country: Germany
facility: Neurology, University Hospital Bonn
city: Frankfurt an der Oder
country: Germany
facility: Hematology, Klinikum Frankfurt/Oder
city: Heidelberg
country: Germany
facility: Hematology, University Hospital Heidelberg
city: Munich
country: Germany
facility: Klinikum Grosshadern, University Hospital Munich
Study officials:
affiliation: Charite University, Berlin, Germany
name: Agnieszka Korfel, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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).
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.
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.
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.
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.
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.