Lenalidomide in Comb w/Rituximab for Pts w/CD5+/CD20+ Hem Malignancies Who Relapse/Progress After Rituximab
Condition: Lymphocytic Leukemia; Mantle Cell Lymphoma
MeSH terms: Lymphoma, Mantle-Cell
Intervention: Lenalidomide; Rituximab
Intervention description: Lenalidomide was administered orally with escalating doses on 28-days cycles. The first cycle was administered with a starting dose of 2.5 mg daily on days 1-7, 5mg on days 8-14 and 10 mg on days 15-21, followed by seven days off. On cycle 2 and beyond lenalidomide was administered at 20 mg daily on days 1-21.; Rituximab was administered at 375 mg/m^2 intravenously on a weekly basis for the first cycle starting on day 15. Subsequent rituximab doses were administered on day one of cycle 2 and beyond, every 4 weeks. Doses were repeated on 28-day cycles until disease progression or unacceptable toxicity, but were planned for 12 cycles.
Intervention MeSH terms: Rituximab; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this research is to evaluate the use of Rituximab in combination with Revlimid
      in the treatment of refractory Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia
      (CLL). Revlimid® is a drug that changes the immune system and it may also get in the way with
      the growth of tiny blood vessels that help support tumor growth. Therefore, in theory, it may
      reduce or prevent the growth of cancer cells. Revlimid® is approved by the Food and Drug
      Administration (FDA) for the treatment of specific types of Myelodysplasia syndrome (MDS) and
      Multiple Myeloma, two different types of blood cancer. It is currently being tested in a
      variety of cancer conditions. In this case it is considered experimental.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have histologically or cytologically confirmed CD5+/CD20+ B-Cell Chronic Lymphocytic
             Leukemia or Mantle Cell Lymphoma

          -  Meet the following CLL criteria to participate in this study:

               -  Absolute lymphocyte count > 5000/μL

               -  CD20+ and CD5+

               -  Atypical cells representing < 55% on the peripheral smear

               -  Bone marrow lymphocytes ≥ 30%

               -  Or previous confirmed diagnosis of CLL/small lymphocytic lymphoma (SLL) with less
                  than 5000/μl or less than 30% lymphocytes in BM

          -  CLL Patients are eligible if they have stage III or IV disease. Patients with stage 0,
             I or II disease will be eligible if they have evidence of active disease defined as
             one or more of the following signs/symptoms:

               -  Documented weight loss of ≥ 10% over a six month period

               -  Febrile episodes of 38 degrees Celsius (100.5 degrees F) or greater for greater
                  than 2 weeks without evidence of infection

               -  Massive or progressive splenomegaly defined as > 6 cm below the left costal
                  margin

               -  Massive (> 10 cm in longest diameter) or progressive lymphadenopathy

          -  Patients with progressive lymphadenopathy will need a biopsy of the lymphadenopathy
             within the previous six months to ensure that the disease entity remains chronic
             lymphocytic leukemia. Lymph node biopsy can be deferred if the patient does not have
             superficial lymphadenopathy that is easily accessible by surgery or by CT guided
             biopsy.

          -  The diagnosis of MCL is based upon the National Comprehensive Cancer Network (NCCN)
             guidelines. The patient's will have biopsy proven CD5+/CD20+/CD23- mantle cell
             lymphoma with the characteristic cytogenetic abnormality t(11;14) or a cyclin D1
             positive immunophenotype. If malignancy is CD23+ but FISH positive for t(11;14),
             diagnosis of mantle cell lymphoma can be made. Patients with mantle cell lymphoma
             require appropriate staging which would include upper and lower endoscopy within 2
             months of enrollment per NCCN guidelines without additional treatment since the
             endoscopies.

          -  Patients with MCL and CLL will be eligible if they have relapsed or progressive
             disease after Rituximab therapy or a combination therapy including Rituximab. Any
             other number of previous treatments is allowed including autologous or allogeneic bone
             marrow transplantation. Patients who are younger than age 65 who have not had a bone
             marrow transplant must be ineligible or have declined a bone marrow (BM) transplant to
             participate in this study. Although a transplant is not the standard of care for this
             patient population, it does provide the best opportunity for a cure.

          -  Anticipated life expectancy of > 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Baseline organ and marrow function as follows:

               -  Absolute neutrophil count ≥1,500/µL

               -  Platelets ≥50,000/µL

               -  Total bilirubin ≤2.0 mg/dL (34 µmol/L)

               -  aspartic transaminase (AST)/alanine transaminase (ALT) ≤2.5 X institutional upper
                  limit of normal(ULN)

               -  Creatinine < institutional ULN OR

               -  Creatinine clearance ≥60 mL/min/m² for patients with creatinine levels above
                  institutional ULN

          -  All study participants must be registered into the mandatory RevAssist® program, and
             be willing and able to comply with the requirements of RevAssist®. Women of
             childbearing potential, and men with a partner of childbearing potential must follow
             pregnancy test and birth control guidelines outlined for this study.

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Patients with uric acid levels > ULN at baseline must be corrected to ≤ULN prior to
             the initiation of study therapy.

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering study or those who have not recovered
             from adverse events due to agents administered more than 4 weeks earlier.

          -  May not be receiving any other investigational agents

          -  Known brain metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to lenalidomide and/or thalidomide

          -  Prior desquamating (blistering) rash with thalidomide

          -  Neuropathy ≥ grade 2

          -  Uncontrolled intercurrent illness including (not limited to) ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Women currently pregnant or breastfeeding

          -  Known seropositive for or active viral infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
             seropositive because of hepatitis B virus vaccine are eligible.

          -  History of another malignancy besides CLL or MCL who have been disease-free ≤ 3 years
             with exception of basal cell or squamous cell carcinoma of skin or carcinoma in situ
             of cervix or breast

          -  Any serious medical condition or psychiatric illness that will prevent patient from
             signing the informed consent form or will place the patient at unacceptable risk if
             he/she participates in the study

          -  Prior use of lenalidomide

          -  Prior severe hypersensitivity to Rituximab or other murine products