Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma
Condition: CD20+, B-cell Lymphomas; Mantle Cell Lymphoma; Non-Mantle Cell Low Grade B Cell Lymphomas (SLL/CLL); Transformed Lymphoma/DLBCL/PMBCL; Hodgkin's Disease; Gray Zone Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Hodgkin Disease
Intervention: Everolimus; Rituximab
Intervention description: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL.; 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)
Intervention MeSH terms: Rituximab; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.