Rapid Infusion of Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Ofatumumab
Intervention description: The first dose of ofatumumab administered on Day 1 will be 300 mg to minimize infusion reactions. If the initial 300 mg dose of ofatumumab is well-tolerated, without occurrence of any infusion-associated AEs of >= grade 3, on Day 3 ofatumumab will increase to 1000 mg IV. If the Day 3 dose was well-tolerated (i.e., no infusion-associated AE >= grade 3), on Day 8 the ofatumumab dose will escalate to 2000 mg IV. To achieve the primary endpoint for this study, 20% of the 2000 mg ofatumumab dose only will be administered over the first 30 minutes and if tolerated the remaining 80% of the dose will be infused over the remaining 1.5/hours of each treatment. Ofatumumab doses, weeks 3-8, will remain at 2000 mg IV with no further dose escalations. If the Day 8 (Week 2) dose is tolerated all subsequent doses may be infused in the same manner.
Intervention MeSH terms: Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Lymphocytic Leukemia; Ofatumumab; Rapid Infusion

Summary:

      This is a Phase II, single-arm study of ofatumumab investigating the safety of an accelerated
      infusion schedule of ofatumumab in patients who have received at least one prior therapy for
      CLL. The primary endpoint is to evaluate the number of subjects able to complete infusion
      number 3 (2000 mg) within 15 minutes of the planned time.
    

Eligibility criteria:

        Inclusion Criteria:

          1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) according to International Workshop
             on CLL Working Group (IWCLL WG) Diagnostic Criteria.

          2. Have received at least one prior therapy for CLL.

             •If previously treated with ofatumumab must have achieved at least a partial response
             (PR) and maintained PR for >= 6 months.

          3. Requires treatment according to IWCLL-Working Group guidelines.

          4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) <=1.

          5. Laboratory parameters <=7 days prior to treatment initiation:

               1. Creatinine <= 1.5 mg/dL upper limit normal (ULN)

               2. Aspartate amino transferase (AST) or alanine amino transferase (ALT) <= 3.0 x ULN

               3. Alkaline phosphatase (ALP) <= 3.0 x ULN

               4. Total Bilirubin level of < 1.5 mg/dL x the institutional ULN unless secondary to
                  Gilbert's disease (or pattern consistent with Gilbert's)

          6. Hepatitis B sAg negative and HepB cAb negative. Note: Patients who are HepB sAg
             negative but are HepB cAb positive (regardless of HepB sAb status) will NOT be
             allowed.

          7. Women of childbearing potential must have a negative serum pregnancy test performed
             <=72 hours prior to start of treatment. Women of childbearing potential or men with
             partners of childbearing potential must use effective birth control measures during
             treatment. If a woman becomes pregnant or suspects she is pregnant while participating
             in this study, she must agree to inform her treating physician immediately.

          8. Accessible for treatment and follow-up.

          9. Able to understand the nature of this study, give written informed consent prior to
             study entry, and comply with study requirements.

         10. No prior antibody therapy for CLL within the previous 3 months.

        Exclusion Criteria:

          1. Previous treatment with ofatumumab that resulted in a Grade 3 or 4 infusion reaction.

          2. Treatment for CLL within last 4 weeks. (Patients who have received steroids or IVIG
             for autoimmune complications of CLL are eligible).

          3. Current active hepatic or biliary disease (with the exception of patients with
             Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver
             disease, per assessment by the treating physician).

          4. Active bacterial or viral infection or infection requiring intravenous antibiotic
             treatment at the time of accrual.

          5. Central nervous system lymphoma/CLL.

          6. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richter's
             transformation).

          7. History of other malignancy <= 2 years of study entry which could affect compliance
             with the protocol or interpretation of results. History of curatively treated basal or
             squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade,
             early-stage, localized prostate cancer treated surgically with curative intent, ductal
             carcinoma in situ (DCIS) of the breast treated with curative intent, are generally
             eligible.

          8. Active hepatitis B or C or known HIV positive.

          9. Treatment with any known non-marketed drug substance or experimental therapy within 5
             terminal half lives or 4 weeks prior to visit 1, whichever is longer.

         10. History of significant cerebrovascular disease in the past 6 months or ongoing event
             with active symptoms or sequelae.

         11. Clinically significant cardiac disease including unstable angina, acute myocardial
             infarction (within 6 months of enrollment), congestive heart failure (NYHA III-IV),
             and arrhythmia unless controlled by therapy, with the exception of extra systoles or
             minor conduction abnormalities.

         12. 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.