***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: This open-label , phase 1 study evaluated the effects of ofatumumab on QTc intervals , safety , efficacy , B-cell and neutrophil counts , complement levels , and cytokine and chemokine concentrations .  Fourteen patients with fludarabine-refractory chronic lymphocytic leukemia received 12 ofatumumab infusions . A higher maximum infusion rate of 400 mL/h was tested at the first two doses and was well tolerated . The 43 % overall response rate was similar to previous data ( 42–51 % ) . B-cell depletion was observed along with complement consumption ; median C2 and CH50 levels appeared lower during monthly dosing in patients who responded . Responding patients appeared to have higher median levels of certain pro-inflammatory cytokines and lower median levels of certain immunotolerant cytokines than patients who did not respond . Ofatumumab-induced complement-dependent cytotoxicity activity can be detected clinical ly by measuring complement and may be associated with clinical activity . The potential relationship between changes in complement or cytokines and clinical response to ofatumumab warrants further study We report the largest retrospective , phase IV non-interventional , observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia . Total number of patients was 103 ; median age was 65 years ( range 39–85 ) . Median number of prior lines of therapy was 4 ( range 1–13 ) , including , in most cases , rituximab- , fludarabine- and alemtuzumab-based regimens ; 13 patients had been allografted . Of 113 adverse events , 28 ( 29 % ) were considered to be directly related to ofatumumab  . Grade 3–4 toxicities included neutropenia ( 10 % ) , thrombocytopenia ( 5 % ) , anemia ( 3 % ) , pneumonia ( 17 % ) , and fever ( 3 % ) . Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy . On an intention-to-treat analysis , the overall response rate was 22 % ( 3 complete response , 1 incomplete complete response ) . Median progression-free and overall survival times were 5 and 11 months , respectively . This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia . The complete response rate , however , was low . Therefore , treatment with ofatumumab should be moved to earlier phases of the disease . Ideally , this should be done in combination with other agents , as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine . This study is registered at clinical trials.gov identifier:01453062 There are limited data on retreatment with monoclonal antibodies ( mAb ) in patients with chronic lymphocytic leukaemia ( CLL ) . In a pivotal study , ofatumumab ( human anti‐CD20 mAb ) monotherapy demonstrated a 47 % objective response rate ( ORR ) in fludarabine refractory CLL patients . From this study , a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions ( induction treatment period ) , followed by monthly infusions for up to 2 years ( maintenance treatment period )  . The ORR after 8 weeks of induction retreatment was 45 % and 24 % had continued disease control after maintenance at 52 weeks . Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study . Response duration was 24·1 months vs. 6·8 months ; time to next therapy was 14·8 months vs. 12·3 months ; and progression‐free survival was 7·4 months vs. 7·9 months ( medians ) . Upon retreatment , 72 % had infusion reactions , mostly Grade 1–2 . Three patients had fatal infections . In summary , ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile Objectives Ofatumumab is a human IgG1κ monoclonal antibody that targets a membrane proximal epitope encompassing the small and large loops of CD20 . This Phase I study evaluated the safety , tolerability , efficacy and pharmacokinetics of ofatumumab monotherapy in Japanese patients with relapsed/refractory B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma . Methods Ofatumumab was administered intravenously weekly for a total of eight doses ( dose escalation : 500 and 1000 mg ) . Six patients ( two chronic lymphocytic leukemia and four small lymphocytic lymphoma ) were enrolled into two dose cohorts ( 500 mg , three patients ; 1000 mg , three patients ) . All six patients received 300 mg ofatumumab at the first infusion and either 500 or 1000 mg at seven subsequent weekly infusions . Results No dose-limiting toxicities or serious adverse events were observed . Grade 3–4 adverse events observed were grade 3 lymphocytopenia ( n = 1 ) and neutropenia ( n = 1 ) . Grade 1–2 infusion-related adverse events leading to temporary interruption of ofatumumab infusion were observed in all six patients on the first infusion day , and all patients completed the planned eight infusions . The overall response rate was 50 % ( 3/6 ) . Conclusions Ofatumumab was well tolerated at doses up to 1000 mg and showed preliminary evidence of activity in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma , warranting further investigations . This study was registered at Clinical Trials.gov ( NCT00742144 ) Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib , availability of nonchemotherapy based therapies is desired . Given the 58 % response rate ( 1996 NCI‐WG criteria ) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab , we initiated a phase II trial examining response , safety , and progression‐free survival ( PFS ) of ofatumumab as front‐line monotherapy . Patients enrolled included untreated , symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy . Two cohorts were enrolled sequentially examining either 1 g ( 33 patients ) or 2 g ( 44 patients ) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months . Patients receiving 1 g were older than those receiving 2 g , but there were no significant differences in other clinical characteristics . The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89 % ( 1996 NCI‐WG criteria ) , respectively ( 54 and 68 % , respectively , using 2008 IWCLL criteria ) . All but two responses were partial . The 24‐month estimated PFS rates were 46 and 78 % , respectively . Response and PFS was lower in del(17p ) and del(11q ) CLL patients . Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high‐risk cytogenetics . Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity . Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well‐tolerated and active regimen , particularly with the 2 g of ofatumumab . Am . J. Hematol . 91:1020–1025 , 2016 . © 2016 Wiley Periodicals , Safety and efficacy of the fully human anti-CD20 monoclonal antibody , ofatumumab , was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia . Three cohorts of 3 ( A ) , 3 ( B ) , and 27 ( C ) patients received 4 , once weekly , infusions of ofatumumab at the following doses : ( A ) one 100 mg and three 500 mg ; ( B ) one 300 mg and three 1000 mg ; ( C ) one 500 mg and three 2000 mg . Sixty-seven percent of the patients were Binet stage B , and the median number of previous treatments was 3 . The maximum tolerated dose was not reached . The majority of related adverse events occurred at first infusion , and the number of adverse events decreased at each subsequent infusion . Seventeen ( 51 % ) of 33 patients experienced infections , 88 % of them of grade 1 - 2 . One event of interstitial pneumonia was fatal ; all other cases resolved within one month . The response rate of cohort C was 50 % ( 13/26 ) , one patient having a nodular partial remission and 12 patients partial remission . In conclusion , ofatumumab was found to be well tolerated in patients with chronic lymphocytic leukemia ( CLL ) in doses up to 2000 mg . Preliminary data on safety and objective response are encouraging and support further studies on the role of  ofatumumab in CLL patients . This trial was registered at www . clinical trials.gov as no. NCT00093314 PURPOSE New treatments are needed for patients with fludarabine- and alemtuzumab-refractory ( FA-ref ) chronic lymphocytic leukemia ( CLL ) or patients with fludarabine-refractory CLL with bulky ( > 5 cm ) lymphadenopathy ( BF-ref ) who are less suitable for  alemtuzumab treatment ; these groups have poor outcomes with available salvage regimens . Ofatumumab ( HuMax-CD20 ) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule . We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL . PATIENTS AND METHODS Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period ( dose 1 = 300 mg ; doses 2 to 12 = 2,000 mg ) ; response by an independent review committee ( 1996 National Cancer Institute Working Group criteria ) was assessed every 4 weeks until week 24 and then every 3 months until month 24 . RESULTS This planned interim analysis included 138 treated patients with FA-ref ( n = 59 ) and BF-ref ( n = 79 ) CLL . The overall response rates ( primary end point ) were 58 % [ corrected ] and 47 % in the FA-ref and BF-ref groups , respectively . Complete resolution of constitutional symptoms and improved performance status occurred in 57 % and 48 % of patients , respectively . Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group , respectively , and 5.9 and 15.4 months in the BF-ref group , respectively . The most common adverse events during treatment were infusion reactions and infections , which were primarily grade 1 or 2 events . Hematologic events during treatment included anemia and neutropenia . CONCLUSION Ofatumumab is an active , well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL BACKGROUND Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia . We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia . METHODS This open-label , multicentre , r and omised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment . Eligible patients had a WHO performance status of 0 - 2 , had a response assessment within the previous 3 months , did not have refractory disease , autoimmune haemolytic anaemia requiring treatment , chronic or active infection requiring treatment , and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant . Using a r and omisation list generated by a central computerised system and an interactive voice recognition system , we r and omly assigned ( 1:1 ) patients to receive ofatumumab ( 300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years ) or undergo observation . R and omisation was stratified by number and type of previous treatment and remission status after induction treatment ( block size of four ) . Treatment assignment was open label . The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population . We report the results of a prespecified interim analysis after two-thirds of the planned study events ( disease progression or death ) had happened . This trial is closed to accrual but follow-up is ongoing . This trial is registered with Clinical Trials.gov , number NCT00802737 . FINDINGS Between May 6 , 2010 , and June 19 , 
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The pooled toxicity analysis showed that Ofatumumab-based therapy was associated with an increased risk of infusion-related reaction but decreased risk of thrombocytopenia and anemia compared with non-Ofatumumab-based therapy .
Moreover , infections , and infusion-related reaction occurred more frequently in participants with single Ofatumumab studies .
Discussion : Our analysis showed PFS was statistically significantly improved with Ofatumumab-based treatments ( including Ofatumumab alone , Ofatumumab plus chemotherapy ) for CLL compared with observation or chemotherapy-based regimen groups .
Ofatumumab had no statistically significant improvement on the OS of patients with CLL .
The Ofatumumab-based therapy could generally decrease the risk of adverse effects except infusion-related reaction and infections