Bendamustine and Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Non-Hodgkin's Lymphoma (NHL)

Phase I/II Study With Bendamustine and Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Non-hodgkin's Lymphoma (NHL) Not Eligible for High Dose Chemotherapy and Autologous/Allogeneic Stem Cell Transplantation

The purpose of this study is to assess the safety, tolerability and activity of the combination of bendamustine and rituximab in patients with relapsed/refractory mantle cell lymphoma who are not eligible for high dose chemotherapy and autologous/allogeneic stem cell transplantation.

Inclusion Criteria:

• Age 18 years or older
• Mantle Cell Lymphoma according to REAL/WHO classification
• First or second relapse or alternatively progression during therapy. Previous use of Bendamustine is permitted, if the patient has reached at least partial remission and progression occured more than 6 months after therapy. Previous high dose chemotherapy with auto-SCT is permitted, if the patient has reached at least partial remission and progression occured more than 12 months after therapy.
• Patients must not be eligible for high dose chemotherapy with auto-SCT or allo-SCT.
• Adequate bone marrow function (hemoglobin > 9g/dl, platelet count >100/nL, absolute neutrophil count >1,5 /nL)
• WHO/ECOG Performance Status 0-2
• Measurable disease (two perpendicular diameters by either physical or radiological examination)
• Life expectancy ≥ 3 weeks
• Written informed consent

Exclusion Criteria:

• Prior treatment with any m-TOR Inhibitor
• Unstable or severe uncontrolled medical condition (e.g. severe congestive heart failure, myocardial infarction within the past 6 months, severe, uncontrolled arterial hypertension, renal insufficiency requiring hemodialysis, severe pulmonary disease, severe diabetes)
• Abnormal liver function: transaminases or total bilirubin > 2 x upper limit of normal (ULN)
• Abnormal renal function: serum creatinine > 2 x upper limit of normal
• Previous malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix.
• Concurrent treatment with strong inhibitors of CYP3A4 and/or inducers of CYP3A4
• Pregnant or breastfeeding women (negative pregnancy test not older than 7 days is required for women of fertile age). Men and women of child-bearing potential must agree to use adequate contraception (i.e. failure rate < 1% p.a. )
• Major surgery within 4 weeks before study entry; minor procedures (e.g. Implantation i.v. port catheter, Lymphnode biopsy) within 1 week before study entry
• Previous therapy with any investigational agents within 28 days before study entry
• Concomitant immunotherapy (e.g. Rituximab) or Chemotherapy other than Bendamustine. Use of systemic steroids should be documented and the Principal Investigator be informed.
• Central nervous system (CNS) lymphomatous involvement
• HIV positivity
• Current or chronic hepatitis B or hepatitis C infection
• Severe psychiatric illness or Individuals that are placed in an institution due to a magisterial or judiciary command.
• Inability to comply with study requirements