Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL)
Condition: CLL
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Ofatumumab/HDMP
Intervention description: High dose methylprednisolone sodium succinate (HDMP) at 1gm/m2 daily as infusion for 3 consecutive days every cycle.
Ofatumumab 300mg administered Day1 of cycle 1 followed by 12 doses of 1000mg administered based on specific schedule.
Each patient will receive a maximum of 3 cycles (one cycle is 28 days)
Intervention MeSH terms: Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Chronic leukemia; Chronic Lymphocytic Leukemia; Relapsed; Refractory

Summary:

      Patients who have relapsed/refractory CLL and require therapy as per iwCLL guidelines will be
      eligible. Subjects will receive a treatment with ofatumumab and HDMP for three consecutive 4
      week cycles. The primary endpoint is to determine the complete response (CR) to therapy and
      the secondary endpoints will assess the safety and tolerability of the regimen, the impact of
      the treatment on progression free, treatment free, overall survival, and pharmacokinetics of
      ofatumumab. Patients will receive allopurinol for tumor-lysis prophylaxis and antimicrobial
      prophylaxis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Previously treated patients with a diagnosis of CLL

          2. Previous treatment with any monoclonal antibody or chemotherapy regardless of response
             as defined by the iwCLL Working Group Guidelines as evidenced by:

               -  progressive marrow failure as manifested by the development of, or worsening of,
                  anemia and/or thrombocytopenia

               -  massive (i.e. at least 6cm below the left costal margin) or progressive or
                  symptomatic splenomegaly

               -  massive nodes (i.e. at least 10cm in longest diameter) or progressive or
                  symptomatic lymphadenopathy.

               -  progressive lymphocytosis with an increase of more than 50% over a 2-month period
                  or lymphocyte doubling time (LDT) of less than 6 months.

               -  autoimmune anemia and/or thrombocytopenia that is poorly responsive to
                  corticosteroids or other standard therapy (See Section 10.2)

          3. Constitutional symptoms, defined as any one or more of the following disease-related
             symptoms or signs: unintentional weight loss of 10% or more within the previous 6
             months significant fatigue (i.e. ECOG PS 2 or worse, inability to work or perform
             usual activities), fevers higher than 100.5ºF or 38.0ºC for 2 or more weeks without
             other evidence of infection, night sweats for more than 1 month without evidence of
             infection

          4. Subjects must be 18 years of age or older, male or female.

          5. ECOG performance status of 0-2.

          6. Subjects must be able to give informed consent.

          7. Females of child bearing potential(FCBP)† must have a negative serum or urine
             pregnancy test within 10 - 14 days prior to and again within 24 hours of starting
             treatment and agree to use a medically accepted contraceptive method for the duration
             of this study.

        Exclusion Criteria:

          1. Hepatitis BsAg positive, Hepatitis BcAb positive, and Hepatitis C positive patients.

          2. Known HIV positive patients.

          3. Diabetics.

          4. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune
             thrombocytopenia (ITP).

          5. Screening laboratory values within these ranges: platelets <50 x 109/L, neutrophils
             <1.0 x 109/L, creatinine >2.0 times upper normal limit,total bilirubin >1.5 times
             upper normal limit (unless a known history of Gilbert's disease), ALT >2.5 times upper
             normal limit (unless due to disease involvement of liver), alkaline phosphatase >2.5
             times upper normal limit (unless due to disease involvement of the liver or bone
             marrow)

          6. Inability to provide informed consent.

          7. Concurrent malignancy (excluding basal and squamous cell skin cancers).

          8. Active fungal, bacterial, and/or viral infection.

          9. History of peptic ulcer disease resulting in GI bleeding within the last 6 months.

         10. Untreated metabolic disorders such as hypothyroidism and Cushing's disease.

         11. History of steroid-induced psychosis.

         12. Estimated life expectancy of less than 3 months by the investigator's best clinical
             judgment.

         13. Serious medical condition that would render the subject medically unstable.

         14. Women who are pregnant or breast-feeding.

         15. History of Pancreatitis.

         16. History of Diverticulitis.

         17. Patients with known hypersensitivity to ofatumumab or known history of anaphylaxis to
             Rituximab or alemtuzumab.

         18. Concurrent use of other anti-cancer agents or treatments.

         19. Subjects 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).