Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma
Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma
This research is being done to determine if combining an investigational drug called
 Everolimus with Rituximab can reduce the risk of your cancer from returning after high dose
 chemotherapy.
Everolimus is a pill that interferes with lymphoma cell growth by blocking a cellular pathway
 important in causing cancer cells to grow, called mTor. Rituximab is an intravenous
 medication that specifically attacks a protein commonly found on lymphoma cells called CD20.

 Rituximab is already widely used to treat multiple forms of lymphoma. Moreover, continuing
 rituximab after the completion of chemotherapy is already commonly used to help patients stay
 in remission longer. Everolimus has been shown in many types of relapsed lymphoma to decrease
 the size of lymph nodes by itself. Everolimus is approved by the Food and Drug Administration
 (FDA) for the treatment of advanced kidney cancer and subependymal giant cell astocytoma. It
 is not approved for use in lymphoma. The use of everolimus in this research study is
 investigational. The word "investigational" means that everolimus is not approved for
 marketing by the Food and Drug Administration (FDA). The FDA is allowing the use of
 everolimus in this study.

 The combination of everolimus and rituximab for 1 year after high dose therapy is also new.
 We believe the combination of these medications right after your chemotherapy will be more
 effective in attacking your remaining cancer before they have time to re-grow.

 The usual treatment of lymphoma after high-dose chemotherapy is observation. After your body
 has fully recovered from the effects of the chemotherapy, you will receive everolimus daily
 for one year and IV rituximab four times during that year.
Inclusion Criteria:

 -  Age >18 years of age

 -  ECOG performance status ≤ 2

 -  INR ≤ 2

 -  Adequate renal and hepatic function defined as a serum creatinine <2.0mg/dL, total
 bilirubin <5mg/dL, and AST and ALT ˂ 2.5 ULN.

 -  Platelet count >75 x 109/L

 -  Hemoglobin >10mg/dL

 -  ANC >3.0x109/L

 -  Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L and fasting triglycerides ≤ 2.5 x
 ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only
 be included after initiation of appropriate lipid lowering medication.

 -  A willingness to use an accepted and effective method of birth control for sexually
 active women of childbearing potential during the study and for 8 weeks after the end
 of study drug treatment.

 -  Ability to sign informed consent

 Exclusion Criteria:

 Patient who have previously received an mTor inhibitor

 -  Patients who are pre-terminal or moribund

 -  Patients currently receiving anticancer therapies or who have received anticancer
 therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation
 therapy, antibody based therapy, etc.)

 -  Uncontrolled diabetes mellitus as defined by HbA1c>8% despite adequate therapy.
 Patients with a known history of impaired fasting glucose or diabetes mellitus (DM)
 may be included, however blood glucose and antidiabetic treatment must be monitored
 closely throughout the trial and adjusted as necessary

 -  Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
 inhaled cortosteroids are allowed

 -  Patients who have received live attenuated vaccines within 1 week of start of
 Everolimus and during the study. Patient should also avoid close contact with others
 who have received live attenuated vaccines. Examples of live attenuated vaccines
 include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
 varicella and TY21a typhoid vaccines;

 -  Patients who have a history of another primary solild malignancy, with the exceptions
 of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast
 from which the patient has been disease free for ≥3 years;

 -  Patients with a history of non-compliance to medical regimens or who are considered
 potentially unreliable or will not be able to complete the entire study;

 -  Patients with active bacterial or fungal infections requiring oral or intravenous
 antimicrobials are not eligible until resolution of the infection

 -  Female patients who are pregnant or breast feeding, or of reproductive potential whoe
 are not using effective birth control methods. Adequate contraception must be used
 throughout the trial and for 8 weeks after the last dose of study drug.

 -  Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
 contraception, during the study and for 8 weeks after the end of treatment

 -  Patients with known intolerance to rituximab

 -  Known history of HIV or Hepatitis C

 -  Active Hepatitis B as defined by seropositivity for hepatitis B surface antigen.
 Subjects with positive hepatitis B core antibody titers and normal liver transaminases
 are allowed provided that prophylaxis is administered per institutional guidelines.
 Please see Addendum 8 for the action to be taken for patients with positive baseline
 hepatitis B results.