Temsirolimus in Recurrent Primary Central Nervous System (CNS) Lymphoma

NCT00942747 | Unknown Phase 2

• 2 other identifiers: TemPCNSLEudraCT 2009-011277-33
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

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.

Conditions

Recurrent or Refractory Primary CNS Lymphoma

Keywords

temsirolimus, primary CNS lymphoma, PCNSL, salvage treatment

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Weeks 4, 12, every 12 weeks thereafter

Secondary Outcomes (3)

• Safety

  continuous

• Time to progression of disease

  Weeks 4, 12, every 12 weeks thereafter or upon clinical suspicion of disease progression

• Penetration of temsirolimus into cerebrospinal fluid

  Weeks 1, 4 and 12

Study Arms (1)

Temsirolimus

EXPERIMENTAL

Weekly IV temsirolimus

Drug: temsirolimus

Interventions

temsirolimus 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

Also known as: Torisel, CCI-770

Temsirolimus

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Pfizer: collaborator

Study Sites (6)

Charité Campus Benjamin Franklin

Berlin, 12200, Germany

RECRUITING

Neurology, Knappschaftskrankenhaus Bochum, Bochum University

Bochum, 44892, Germany

RECRUITING

Neurology, University Hospital Bonn

Bonn, 53127, Germany

RECRUITING

Hematology, Klinikum Frankfurt/Oder

Frankfurt (Oder), 15236, Germany

NOT YET RECRUITING

Hematology, University Hospital Heidelberg

Heidelberg, 69120, Germany

NOT YET RECRUITING

Klinikum Grosshadern, University Hospital Munich

Munich, 81377, Germany

RECRUITING

Related Publications (7)

• 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.

  PMID: 18094423 BACKGROUND

• 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).

  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.

  PMID: 19581539 BACKGROUND

• 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.

  PMID: 18543327 BACKGROUND

• 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.

  PMID: 15983389 BACKGROUND

• 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.

  PMID: 17161912 BACKGROUND

• 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.

  PMID: 26976424 DERIVED

MeSH Terms

Conditions

Recurrence

Interventions

temsirolimus

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Agnieszka Korfel, MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agnieszka Korfel, MD

CONTACT

+49308445; agnieszka.korfel@charite.de

Philipp Kiewe, MD

CONTACT

+493064499; philipp.kiewe@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. Agnieszka Korfel

Study Record Dates

• First Submitted: July 20, 2009
• First Posted: July 21, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2014
• Last Updated: April 17, 2013

Record last verified: 2013-04

Locations

DE (6)