Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL
Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL
The main purpose of this study is to examine how two separate groups of 17p deletion Chronic
 lymphocytic leukemia (CLL) participants respond to sequential treatment with this particular
 combination of drugs. The two groups are those participants who have previously received
 treatment for their CLL and those who have not yet received any treatment. The combination of
 drugs is Ofatumumab and High-Dose Methylprednisolone (HDMP) first followed by Ofatumumab and
 Alemtuzumab. All three drugs are FDA approved and have known activity in treating 17p CLL. We
 hope that by combining these drugs together in this study, they will have more benefit than
 each one alone and that the subjects' CLL will be significantly impacted.
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups
 received the same therapy.

 Part A: Ofatumumab + HDMP 2-4 cycles Part B: Ofatumumab + Alemtuzumab 1-6 cycles Part C:
 Maintenance with Ofatumumab + Alemtuzumab up to 2 years

 Between days 15-22 of Cycle 2 of Part A, participants are restaged. Participants who achieve
 nodal complete response discontinue Part A therapy and undergo minimal residual disease (MRD)
 assessment to guide the decision whether to go to Part B or Part C. The participants with
 persistent disease after 2 cycles of Part A therapy receive 2 more cycles of Part A therapy
 and then undergo another restaging as well as MRD assessment. At restaging, participants with
 minimal disease are eligible for Part C or allogeneic stem cell transplant (SCT) off
 protocol. The remaining participants receive Part B therapy. On Part B, restaging occurs at
 weeks 12 and 18. If MRD negative complete response (CR) status is achieved then therapy is
 discontinued and the primary endpoint evaluation occurs 2 months later. Otherwise with
 persistent disease Part B therapy continues up to 24 weeks and the primary endpoint
 evaluation occurs after Part B therapy is completed. Participants who achieve clinical
 complete response may receive Part C therapy or be observed while waiting SCT.
Inclusion Criteria:

 -  Documented CLL/SLL

 -  17p deletion by FISH in 20% or more nuclei on peripheral blood, bone marrow or lymph
 node

 -  Normal organ function

 Exclusion Criteria:

 -  Pregnant or breast feeding

 -  Current active hepatic or biliary disease

 -  Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
 antiviral treatment such as, but not limited to, chronic renal infection, tuberculosis
 and active Hepatitis C

 -  History of significant cerebrovascular disease in the past 6 months or ongoing event
 with active symptoms or sequelae

 -  Other past or current malignancy. Participants who have been free of malignancy for at
 least 2 years, or who have a history of completely resected non-melanoma skin cancer
 or successfully treated in situ carcinoma are eligible.

 -  Known HIV positive

 -  Clinically significant cardiac disease including unstable angina, acute myocardial
 infarction within 6 months prior to study entry, congestive heart failure, and
 arrhythmia unless controlled by therapy, with the exception of extra systoles or minor
 conduction abnormalities.

 -  Significant concurrent uncontrolled medical conditions 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 subject.

 -  Positive serology for Hepatitis B or C

 -  History of allergic reactions attributed to ofatumumab.