Everolimus Plus Rituximab for Relapsed/Refractory Diffuse Large B Cell Lymphoma
Condition: Diffuse Large B-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Everolimus; rituximab
Intervention description: Taken orally once daily in the morning; Given intravenously on Days 1, 8, 15, and 22 of Cycle 1 then on Day 1 of cycles 2-6
Intervention MeSH terms: Rituximab; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: rituximab; everolimus; DLBCL; mTOR

Summary:

      Everolimus is an oral mTOR inhibitor with demonstrated preliminary efficacy and safety in
      diffuse large B-cell lymphoma (DLBCL) in both preclinical and clinical studies. The purpose
      of this research study is to determine whether Everolimus plus rituximab is safe and
      effective in participants with relapsed or refractory DLBCL. Everolimus is an investigational
      drug that works by blocking a special protein that helps cancer cells grow. The safety and
      effectiveness of Everolimus in the treatment of DLBCL has not yet been fully determined and
      is still investigational. The other drug in this study, rituximab, is approved by the US Food
      and Drug Administration (FDA) for use in patients who have diffuse large B-cell lymphoma and
      certain other types of non-Hodgkin lymphoma. Rituximab is a drug that destroys both normal
      and cancerous B-cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically determined DLBCL that is relapsed or primary refractory after initial
             therapy

          -  Greater than 1 prior line of chemotherapy (including an anthracycline unless
             contraindicated) or immunotherapy. Patients must have relapsed after autologous stem
             cell transplantation, not be eligible for autologous stem call transplantation in the
             judgment of the investigator, or refuse autologous stem cell transplantation. Salvage
             chemotherapy and high dose conditioning for autologous stem cell transplantation count
             as two separate regimens.

          -  Measurable disease that has not been previously irradiated on PET-CT of at least 2cm,
             OR if the patient has had previous radiation to the marker lesion(s), there must be
             evidence of progression since the radiation. Imaging must be completed no greater than
             3 weeks from study enrollment.

          -  ECOG performance status 0-2

          -  18 years of age or older

          -  Life expectancy of greater than 3 months

          -  Adequate Organ and marrow function

          -  Fasting serum cholesterol of 300 mg/dl or less OR 7.75 mmol/L or less AND fasting
             triglycerides 2.5 x ULN or less

        Exclusion Criteria:

          -  Currently receiving anticancer therapies or who have received anticancer therapies
             within 3 weeks of the start of the study drug

          -  Receiving any other investigational agents, or have received investigational agents
             within 4 weeks of beginning treatment

          -  Major surgery or significant traumatic injury within 4 weeks of start of study drug,
             patients who have not recovered from the side effects of any major surgery (defined as
             requiring general anesthesia) or patients that may require major surgery during the
             course of the study

          -  Known leptomeningeal or brain metastases. Imaging or spinal fluid analysis to exclude
             CNS involvement is not required, unless there is clinical suspicion by the treating
             investigator

          -  Known HIV infection

          -  Systemic fungal, bacterial, viral, or other infection not controlled

          -  Prior history of malignancy (except for non-melanoma skin cancer or in situ cervical
             or breast cancer) unless disease free for at least one year. Patients with prostate
             cancer are allowed if PSA is less than 1

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period

          -  Severely impaired lung function defined as DLCO of <60%

          -  Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN

          -  Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
             hepatitis

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of Everolimus

          -  Active bleeding diathesis

          -  Female patients who are pregnant or breastfeeding, or adults of reproductive potential
             who are not using effective birth control methods

          -  Prior treatment with an mTOR inhibitor

          -  Known hypersensitivity to murine antibodies,everolimus,other rapamycin

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study

          -  No chronic treatment with systemic corticosteroids or other immunosuppressive agents.
             Topical or inhaled corticosteroids are permitted