Temsirolimus, Bendamustine and Rituximab for Relapsed Follicular Lymphoma or Mantle Cell Lymphoma

Inclusion Criteria:

* Histologically proven diagnosis of follicular non-Hodgkin's lymphoma grades l, II or IIIA or mantle cell lymphoma (including Cyclin D1 expression) according to the World Health Organization classification
* Documented relapse or progression following at least one but not more than 3 antineoplastic treatments
* At least 1 measurable tumor mass (\>1.5 cm x \>1.0 cm) or bone marrow infiltration
* Subjects 18 years or older
* Status post. high dose therapy or no transplantation option available or patient refuses an aggressive treatment strategy
* Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
* Adequate bone marrow reserve: Platelets of at least 75000/µl, absolute neutrophil count at least 1500/µl. In case of extensive bone marrow infiltration and lower platelet or absolute neutrophil counts, patients can not be included in the phase I part of the trial. In the phase II proportion of the trial patients may be included with a platelet count of more or equal to 50000/µl on the discretion of the investigator, if thrombocytopenia is associated with massive bone marrow infiltration.
* Adequate hepatic and renal function

  * Alanine aminotransferase \<2.5 x upper limit of normal (ULN); Aspartate aminotransferase \<2.5 x ULN, Total bilirubin \<1.5 x ULN
  * Measured or calculated creatinine clearance \>50 mL/min
* Eastern Cooperative Oncology Group \[ECOG\] performance Status 0-2
* Female subject must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum ß-hCG pregnancy test at screening

Exclusion Criteria:

* Lymphoma other than MCL or FL
* Active central nervous System lymphoma. Brain MRI is required only if clinically indicated
* Pregnancy or breast feeding women
* Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinemia)
* Active uncontrolled infections including HIV-positivity, active Hep B or C
* Mental status precluding patient's compliance
* Comedication with strong CYP 3A4/5-inhibitors or -inducers (Appendix 22.7)
* Prior treatment with Temsirolimus
* Known CD20 negativity
* Patients refractory to Bendamustine in a prior treatment line, defined as relapse within 1 year after initiation of first cycle. Exception: termination of treatment prior to third scheduled cycle for reasons other than toxicity.
* Status post allogeneic transplantation
* Peripheral neuropathy or neuropathic pain of Grade 2 or worse
* Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, DCIS of the breast, or other solid tumors curatively treated with no evidence of disease for \>5 years
* Concurrent treatment with another investigational agent. Concurrent participation in non-treatment studies is not excluded.
* Known intolerance to sirolimus or derivates, or Bendamustine or Rituximab.