Ofatumumab, High Dose Methylprednisolone, Ofatumumab and Lenalidomide Consolidative Therapy for Untreated CLL/SLL
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: High Dose Methylprednisolone (HDMP); Ofatumumab; Lenalidomide
Intervention description: HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8.; Ofatumumab infusion will be administered immediately after HDMP.; The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Lenalidomide; Ofatumumab; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: leukemia; lymphoma; consolidative therapy; combination regimen; CLL; SLL

Summary:

      The main purpose of this study is to see if ofatumumab with methylprednisolone followed by
      additional treatment with ofatumumab and lenalidomide can help people with Chronic
      Lymphocytic Leukemia (CLL) get rid of their CLL for a long period of time. Researchers also
      want to find out if the combination of ofatumumab with methylprednisolone followed by
      additional treatment with ofatumumab and lenalidomide is safe and tolerable.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Patients must have histologically or cytologically confirmed CD5+/CD20+ B-Cell chronic
             lymphocytic leukemia or small lymphocytic lymphoma. The diagnosis of CLL is based upon
             the National Comprehensive Cancer Network (NCCN) guidelines. Any outside pathology
             slides used as inclusion criteria for the patient will be reviewed at this institution
             to confirm the diagnosis. The patient must meet all of the following CLL criteria to
             participate in this study: absolute lymphocyte count > 5000/μL; CD20+ and CD5+; Bone
             marrow lymphocytes ≥ 30%; Or previous confirmed diagnosis of CLL/SLL with less than
             5000/μl or less than 30% lymphocytes in bone marrow.

          -  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 6
             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.

          -  Patient has not received any prior treatment for CLL in the past.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry

          -  Laboratory test results within these ranges: Absolute neutrophil count ≥ 1000/mm³;
             Platelet count ≥ 50,000 /mm³; Renal function assessed by calculated creatinine
             clearance ≥ 30ml/min by Cockcroft-Gault formula; Total bilirubin ≤ 1.5 x upper limit
             of normal (ULN); aspartic transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT)
             ≤ 2.5 x ULN; Alkaline phosphatase <2.5 x ULN

          -  Disease free of prior malignancies for ≥ 5 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
             or breast

          -  All study participants must be registered into the mandatory REMS® program, and be
             willing and able to comply with the requirements of REMS®.

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again
             within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be
             filled within 7 days) and must either commit to continued abstinence from heterosexual
             intercourse or begin TWO acceptable methods of birth control, one highly effective
             method and one additional effective method AT THE SAME TIME, at least 28 days before
             she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men
             must agree to use a latex condom during sexual contact with a FCBP even if they have
             had a successful vasectomy.

          -  Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
             intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight
             heparin).

        Exclusion Criteria:

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form

          -  Pregnant or breast feeding females. (Lactating females must agree not to breast feed
             while taking lenalidomide).

          -  Any condition, including the presence of laboratory abnormalities, which places the
             patient at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study

          -  Evidence of laboratory Tumor Lysis Syndrome (TLS) by Cairo-Bishop Definition. Patients
             may be enrolled upon correction of electrolyte abnormalities.

          -  Use of any other experimental drug or therapy within 28 days of baseline

          -  Known hypersensitivity to thalidomide

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs.

          -  Any prior use of lenalidomide

          -  Concurrent use of other anti-cancer agents or treatments

          -  Known seropositive for or active viral infection with human immunodeficiency virus
             (HIV)

          -  Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In
             addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test
             will be performed and if positive the patient will be excluded. Note: If HBcAb
             positive and HBsAb positive, which is indicative of a past infection, the patient can
             be included. Patients who are seropositive because of hepatitis B virus vaccine are
             eligible. Consult with a physician experienced in care & management of subjects with
             hepatitis B to manage/treat subjects who are anti-HBc positive.

          -  Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C
             antibody (HCAb), in which case reflexively perform a HC recombinant immunoblot assay
             (RIBA) on the same sample to confirm the result

          -  Patients who have current active hepatic or biliary disease (with exception of
             patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable
             chronic liver disease per investigator assessment) are ineligible.

          -  Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
             antiviral treatment such as, but not limited to, chronic renal infection, chronic
             chest infection with bronchiectasis, tuberculosis and active Hepatitis C

          -  History of significant cerebrovascular disease in the past 6 months or ongoing event
             with active symptoms or sequelae

          -  Clinically significant cardiac disease including unstable angina, acute myocardial
             infarction within 6 months prior to randomization, congestive heart failure [New York
             Heart Association (NYHA) III-IV], and arrhythmia unless controlled by therapy, with
             the exception of extra systoles or minor conduction abnormalities

          -  Significant concurrent, uncontrolled medical condition including, but not limited to,
             renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
             psychiatric disease which in the opinion of the investigator may represent a risk for
             the patient