Recurrent or Refractory Primary CNS Lymphoma
Conditions
Keywords
temsirolimus, primary CNS lymphoma, PCNSL, salvage 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.
Interventions
DRUGtemsirolimus
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
Sponsors
Pfizer
Charite University, Berlin, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response rate | Weeks 4, 12, every 12 weeks thereafter |
Secondary
| Measure | 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 |
Countries
Germany
Contacts
Primary ContactAgnieszka Korfel, MD
Backup ContactPhilipp Kiewe, MD
Outcome results
None listed