Temsirolimus in Recurrent Primary Central Nervous System (CNS) Lymphoma

Study Overview
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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.

Official Title
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Phase 2 Study of Temsirolimus in Refractory and Recurrent Primary CNS Lymphoma

Conditions
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Recurrent or Refractory Primary CNS Lymphoma

Intervention / Treatment
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* Drug: temsirolimus


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temsirolimus<br>Weekly IV temsirolimus | Drug: temsirolimus<br>* 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<br>* Other names: CCI-770;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | Weeks 4, 12, every 12 weeks thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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temsirolimus, primary CNS lymphoma, PCNSL, salvage treatment