Temsirolimus in Recurrent Primary Central Nervous System (CNS) Lymphoma

NCT ID: NCT00942747

Last Updated: 2013-04-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2014-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Recurrent or Refractory Primary CNS Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Temsirolimus

Weekly IV temsirolimus

Group Type EXPERIMENTAL

temsirolimus

Intervention Type DRUG

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

Interventions

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temsirolimus

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

Intervention Type DRUG

Other Intervention Names

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Torisel CCI-770

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role lead

Responsible Party

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PD Dr. Agnieszka Korfel

PD Dr. Agnieszka Korfel

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Agnieszka Korfel, MD

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

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Charité Campus Benjamin Franklin

Berlin, , Germany

Site Status RECRUITING

Neurology, Knappschaftskrankenhaus Bochum, Bochum University

Bochum, , Germany

Site Status RECRUITING

Neurology, University Hospital Bonn

Bonn, , Germany

Site Status RECRUITING

Hematology, Klinikum Frankfurt/Oder

Frankfurt (Oder), , Germany

Site Status NOT_YET_RECRUITING

Hematology, University Hospital Heidelberg

Heidelberg, , Germany

Site Status NOT_YET_RECRUITING

Klinikum Grosshadern, University Hospital Munich

Munich, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Agnieszka Korfel, MD

Role: CONTACT

+49308445 ext. 4096

Philipp Kiewe, MD

Role: CONTACT

+493064499 ext. 5225

Facility Contacts

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Agnieszka Korfel, MD

Role: primary

+49308445 ext. 4096

Philipp Kiewe, MD

Role: backup

+493064499 ext. 5225

Uwe Schlegel, MD

Role: primary

+49-2342993701

Simone Middelhauve

Role: backup

+49-2342993701

Ulrich Herrlinger, MD

Role: primary

+49-222828719887

Christiane Landwehr

Role: backup

+49-222828719887

Michael Kiel, MD

Role: primary

+4933-55484604

Melanie Binsker

Role: backup

+4933-55484604

Gerlinde Egerer, MD

Role: primary

+49-6221568029

Martina Gronkowski

Role: backup

+49-6221568029

Martin Dreyling, MD

Role: primary

+498970955202

Carmen Carlucci

Role: backup

+498970955202

References

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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.

Reference Type BACKGROUND
PMID: 18094423 (View on PubMed)

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).

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 19581539 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18543327 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15983389 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17161912 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26976424 (View on PubMed)

Other Identifiers

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EudraCT 2009-011277-33

Identifier Type: -

Identifier Source: secondary_id

TemPCNSL

Identifier Type: -

Identifier Source: org_study_id

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