A Randomized Phase 4 Study Comparing 2 Intravenous Temsirolimus (TEMSR) Regimens in Subjects With Relapsed, Refractory Mantle Cell Lymphoma

The subject must meet all of the following criteria to be enrolled in the study:;1. MCL confirmed locally with histology, immunophenotype, and cyclin D1 analysis.;2. Male or female subjects aged 18 years or older.;3. Refractory to or relapsed from 2 to 7 prior therapies, which may include HSCT (ie, induction + consolidation + maintenance).;4. Prior treatment with an alkylating agent and an anthracycline and rituximab, individually or in combination.;5. Measurable disease in an area of no prior radiotherapy or clear progression in an area that was previously irradiated;6. Adequate organ and marrow function obtained within 2 weeks prior to first dose administration of TEMSR as defined by the following:;• Absolute neutrophil count (ANC) >= 1,000/µL;• Platelet (PLT) >=75,000/µL (>= 50,000/µL is allowed if with bone marrow involvement);• Hemoglobin >= 8 g/dL;• Total bilirubin <= 1.5 x upper limit normal (ULN) (if abnormal, direct bilirubin must be <= 1.5 x ULN);• Aspartate aminotransferase (AST) <= 3 x ULN (<= 5 x ULN is allowed if with liver involvement);• Serum creatinine <= 2 x ULN;• Fasting serum cholesterol <= 350 mg/dL (9.01 mmol/L);• Triglycerides <= 400 mg/dL (4.5 mmol/L);• Glycosylated hemoglobin (Hgb A1c) <10% (optimal therapy permitted);• Other laboratory values all common toxicity criteria (CTC) version 3.0 grade <= 2 unless related to lymphomatous organ involvement.;7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.;8. For women of child bearing potential, a negative serum pregnancy test prior to first dose administration of any investigational agen (ie: Desipramine and/or TEMSR). Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

Presence of any of the following criteria will exclude the subject from enrollment in the study:;1. Subjects who are <= 6 months from allogeneic HSCT and who are on immunosuppressive therapy or have evidence of graft host disease.;2. Prior investigational therapy within 3 weeks before first infusion of TEMSR. Investigational therapy is defined as treatment that is not approved for any indication.;3. Treatment within the following time frame relative to first dose administration of TEMSR:;• Chemotherapy, radiotherapy, immunotherapy, or major surgery <= 3 weeks;• Nitrosourea or mitomycin <= 6 weeks;• Radioimmunotherapy <= 8 weeks;• Other nonmyelosuppressive biological response modifiers < 2 weeks.;4. Active central nervous system (CNS) metastases. Subjects with brain metastases are eligible as long as they are clinically stable prior to first dose administration of TEMSR (no significant changes in anticonvulsant doses, mental status,or clinical symptoms related to CNS metastases) after completion of definitive therapy.;5. Current active second malignancy other than nonmelanoma skin cancers and clinically localized prostate cancer. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy with curative intent and are disease-free at least 2 years prior to first dose administration of TEMSR. Subjects with a history of cervical carcinoma in situ, breast ductal carcinoma in situ, or breast lobular carcinoma in situ are considered eligible provided they have completed definitive therapy.;6. Any prior history of noninfectious interstitial pneumonitis / interstitial lung disease.;7. Subjects who are receiving desipramine or have an intolerance to desipramine or other tricyclic antidepressants. (this criterion pertains only to subjects who are participating in the desipramine/PK sub-study);8. Prior treatment with TEMSR or other mTOR inhibitor.;9. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality or cardiac dysfunction that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.;10. Previous history of hypersensitivity to TEMSR, its metabolites (including sirolimus), polysorbate 80, or any other components of TEMSR formulation.;11. Hypersensitivity to antihistimines or subjects who cannot receive antihistimines for other medical reasons.