Study Evaluating Temsirolimus (CCI-779) In Mantle Cell Lymphoma (MCL)

• Drug: Temsirolimus (CCI-779)
  Temsirolimus 175 mg IV once a week for 3 weeks; followed by 75 mg IV once a week
• Drug: Temsirolimus (CCI-779)
  Temsirolimus 175 mg IV once a week for 3 weeks; followed by 25 mg IV once a week
• Drug: Investigator's choice

  Any of the following single agent treatments:

  1. Fludarabine 25 mg/m2 IV over 30 minutes daily for 5 consecutive days, every 28 days or oral administration, as appropriate.
  2. Chlorambucil 0.1 (0.1-0.2) mg/kg PO daily for 3 to 6 weeks as required OR 0.4 (0.3 0.8) mg/kg PO every 21 to 28 days
  3. Gemcitabine 1 gm/m2 IV over 30 minutes on days 1, 8 and 15 every 28 days or day 1 and day 8 every 21 days
  4. Cyclophosphamide 300 (200-450) mg/m2 PO daily for 5 consecutive days every 21 to 28 days, OR 600 (400-1200) mg/m2 IV every 21 to 28 days
  5. Cladribine 5 mg/m2 IV daily for 5 consecutive days, every 28 days for 2-6 cycles depending on response,
  6. Etoposide 50 (50-150) mg/m2 IV daily for 3-5 days every 21 to 28 days OR 100 (50 300) mg/m2 PO daily for 3-5 days every 21 to 28 days
  7. Prednisone 40 (20-60) mg/m2 PO daily or every other day
  8. Dexamethasone 20(20-40) mg PO/IV daily for 5 consecutive days, every 14 - 28 day

• Experimental: A
  Intervention: Drug: Temsirolimus (CCI-779)
• Experimental: B
  Intervention: Drug: Temsirolimus (CCI-779)
• Active Comparator: C
  Intervention: Drug: Investigator's choice

Inclusion Criteria:

• Mantle cell lymphoma (MCL) confirmed with histology, immunophenotype, and cyclin D1 analysis
• Received 2 to 7 prior therapies which may include hematopoietic stem cell transplant (i.e. induction + consolidation + maintenance)
• Prior treatment with an alkylating agent and an anthracycline, rituximab, individually or in combination, and status that is at least one of the following:
• Primary disease refractory to at least 2 regimens;
• Refractory to at least 1 regimen after first relapse;
• Refractory or untreated after second or greater relapse;
• Refractory to first line and relapsed after second line. Chemotherapy combinations may include, but are not limited to: CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisone), R-CHOP (Rituximab, Cyclophosphamide, doxorubicin, vincristine, prednisone), FCM (Fludarabine, cyclophosphamide, mitoxantrone), R-FCM (Rituximab,Fludarabine, cyclophosphamide, mitoxantrone), ICE(Ifosfamide, carboplatin, etoposide), DHAP (Dexamethasone, cisplatin, cytarabine) and hyper-CVAD (Cyclophosphamide, doxorubicin, vincristine, dexamethasone).

Exclusion Criteria:

• Subjects who are less than or equal to six month from allogeneic hematopoietic stem cell transplant and who are on immunosuppressive therapy or have evidence of graft versus host disease
• Prior investigational therapy within 3 weeks of first dose. Investigational therapy is defined as treatment that is not approved for any indication.
• Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth. (Treated CNS metastases must be stable for > 2 weeks prior to Day 1.)