Phase III study of RAD001 adjuvant therapy in poor risk patients with Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 versus matching placebo after patients have achieved complete response with first-line rituximab-chemotherapy

• Drug: RAD001
  RAD001 10 mg (two 5 mg tablets), daily for 12 months
  Other Name: Everolimus
• Drug: Placebo
  Placebo

• RAD001: Experimental
  Intervention: Drug: RAD001
• Placebo: Placebo Comparator
  Intervention: Drug: Placebo

Inclusion Criteria:

Patients with previous histologically confirmed Stage III-IV (or Stage II bulky disease, defined as any tumor mass more than 10 cm in longest diameter), at time of original diagnosis, diffuse large B cell lymphoma (pathology report based on original tumor tissue/lymph node is acceptable for meeting inclusion criteria, but tumor tissue (slides/block) must be available to be sent for central pathology to confirm diagnosis).

Patients defined as poor risk with IPI of 3, 4, or 5 at time of original diagnosis.

Patients age ≥ 18 years old. Patients must have achieved complete remission (CR) based on the revised IWRC (Cheson et al 2007) following first line R-CHOP treatment. Radiation therapy in combination with R-CHOP is acceptable if the radiation therapy ended by the time of R-CHOP completion. Complete remission from R-CHOP must be confirmed by clinical and radiologic evaluation along with bone marrow confirmation (if bone marrow was involved by lymphoma before the R-CHOP treatment). Local pathology report on the bone marrow biopsy is acceptable. If bone marrow was not involved by lymphoma before R-CHOP treatment, then another bone marrow confirmation after R-CHOP is not required.

Patients who received a minimum 6 cycles of R-CHOP treatment and maximum 8 cycles of R-CHOP treatment. Any variation of CHOP (R-CHOP-14, R-CHOP-21) is acceptable. Liposomal doxorubicin is acceptable.

Patients' last treatment with R-CHOP must be 6 to 12 weeks prior to start of study drug.

Patients with ECOG performance status (PS) 0, 1, or 2. Patients willing to provide a portion of his/her tumor tissue from original diagnosis or lymph node to confirm diagnosis.

Exclusion Criteria:

Patients with evidence of disease according to the revised IWRC (Cheson et al 2007) after completion of the first-line R-CHOP treatment, prior to study entry.

Patients receiving ongoing radiation therapy or who received radiation therapy to the residual tumor masses after completing R-CHOP.

Patients who have previously received systemic mTOR inhibitor (sirolimus, temsirolimus, everolimus, etc).

Patients with evidence of current central nervous system (CNS) involvement. Patients who have only had prophylactic intrathecal or intravenous chemotherapy against CNS disease are eligible.

Patients with transformed follicular lymphoma. Patients who received ibritumomab tiuxetan (Zevalin®), in order, to avoid potential delayed kidney toxicities.

Patients who had myelosuppressive chemotherapy or biologic therapy < 3 weeks.