Subcutaneous Alemtuzumab (CAMPATH®, MabCampath®) in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia
Condition: B-Cell Chronic Lymphocytic Leukemia (B-CLL)
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Alemtuzumab; Alemtuzumab
Intervention description: Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated). When escalation to 30 mg is tolerated, all subsequent doses are administered at 30 mg SC 3 times per week at alternating injection sites for up to 18 weeks.
Part 1 of the study: The first 20 patients will be randomized to either Arm 1 (dose escalation) or Arm 2 (no escalation). Part 1 of the study has been completed; no additional patients will be enrolled in Part 1. An assigned review panel has reviewed the safety data from Part 1 and determined that all patients will be enrolled and treated under a no escalation schedule for Part 2 of the study.; Alemtuzumab treatment is started immediately at the 30mg dose (with no escalation period), administered SC at alternating injection sites 3 times per week for up to 18 weeks.
Part 2 of the study: All patients are currently being enrolled under the no escalation schedule for Part 2 of the study. All patients in Part 2 will be treated with 30mg of alemtuzumab (with no escalation period) administered SC (at alternating injection sites) 3 times per week (e.g., Monday, Wednesday, Friday) for up to 18 weeks. Alemtuzumab is to be administered in a supervised medical setting on an outpatient basis for the first three weeks, after which some study centers may allow a home administration option, with one weekly clinic visit. Under the home administration option, alemtuzumab may be administered by the patient or care giver if the patient meets conditions specified in the protocol guidelines for home administration.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CAMPATH; Alemtuzumab; Leukemia; MabCampath; Chronic; Subcutaneous; CLL; C-CLL; Relapsed; Refractory; Chronic Lymphocytic Leukemia

Summary:

      This is a Phase II, open-label, prospective, multicenter study to evaluate the efficacy and
      safety of subcutaneously administered alemtuzumab (CAMPATH, MabCampath) as therapy for
      patients with relapsed or refractory B-CLL who have been previously treated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National
             Cancer Institute Working Group (NCI WG) Criteria.

          -  World Health Organization (WHO) performance status of 0, 1, or 2.

          -  Life expectancy ≥ 12 weeks.

          -  Previous therapy with at least one but no more than 5 regimens (single agent or
             combination regimen). One therapy regimen is defined as consecutive, contiguous cycles
             of the same drug(s) with no treatment interruptions lasting > 3 months.

          -  Patient requires treatment for CLL per the following criteria: -Rai stage III or IV;
             -Rai stage 0-II with at least one of the following - evidence of progressive marrow
             failure as manifested by the development of, or worsening of, anemia and/or
             thrombocytopenia; Massive (i.e. greater than 6 cm below the left costal margin) or
             progressive splenomegaly; Progressive lymphocytosis with an increase of greater than
             50% over a 2-month period or an anticipated doubling time of less than 6 months;
             Lymphocyte count > 100*10^9/L; B symptoms.

          -  More than 3 weeks since prior chemotherapy. Patient must have recovered from the acute
             side effects incurred as a result of previous therapy.

          -  More than 3 weeks since using investigational agents. Patient must have recovered from
             the acute side effects incurred as a result of previous therapy.

          -  Serum creatinine and conjugated (direct) bilirubin less than or equal to 2 times the
             institutional upper limit of normal (ULN) unless secondary to direct infiltration of
             the liver with CLL.

          -  Female patients with childbearing potential must have a negative pregnancy test (serum
             or urine) within 2 weeks of first dose of study drug(s). All patients must agree to
             use an effective contraceptive method while on study treatment, if appropriate, and
             for a minimum of 6 months following study therapy.

          -  Signed, written informed consent (in the US, includes The Health Insurance Portability
             and Accountability Act of 1996 (HIPAA) authorization)

        Exclusion Criteria:

          -  Positive Coombs test and evidence of active hemolysis.

          -  Platelet count less than 50*10^9/L without splenomegaly.

          -  History of anaphylaxis following exposure to rat or mouse derived CDR-grafted
             humanized monoclonal antibodies.

          -  Previously treated with CAMPATH.

          -  Previous bone marrow transplant.

          -  Known central nervous system (CNS) involvement with B-CLL

          -  Active infection, including human immunodeficiency virus (HIV) positive.

          -  Active second malignancy.

          -  Recent documented history (within 2 years) of active tuberculosis (TB), current active
             TB infection, currently receiving anti-tuberculous medication (e.g., INH, rifampin,
             streptomycin, pyrazinamide, or others).

          -  Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive
             hepatitis B serologies. Patients with a positive hepatitis B surface antibody (HBsAb)
             test with a documented history of prior hepatitis B immunization are eligible as long
             as other criteria are met (i.e. negative tests for: hepatitis B surface antigen
             (HBsAg), hepatitis B core antibody (HBcAb) and hepatitis C virus antibody (HCVAb)).

          -  Other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental
             disorders, or major organ malfunction (liver, kidney) that could interfere with the
             patient ability to participate in the study.

          -  Pregnant or nursing women.

          -  Cytomegalovirus (CMV) positive by polymerase chain reaction (PCR) (above the level of
             detection). A patient that is PCR positive will require treatment to reduce the viral
             load to a non-detectable level; but such a patient may be considered for study entry
             once the infection has been treated.

          -  Medical condition requiring chronic use of oral corticosteroids at a dose higher than
             physiologic replacement.