Gribben 2005

Methods	Randomisation: 2 arms: up to 6 cycles Flu‐R versus up to 6 cycles Flu‐Cam Recruitment period: not stated Median follow‐up time: not stated
Participants	Eligibility criteria: relapsed B‐cell CLL patients after failure to first‐line treatment Patients recruited (N = 12): Flu‐R (N = 8): withdraws or exclusions not stated Flu‐Cam (N = 4): withdraws or exclusions not stated Mean age: 67 years, no data for each arm Gender: 7 male, 5 female no data for each arm Stage of disease (Rai stage group): stage I‐II: Flu‐R: 1 patients (12.5%); Flu‐Cam: 2 patients (50.0%) stage III‐IV: Flu‐R: 7 patients (87.5%); Flu‐Cam: 2 patients (50.0%) Country: not stated
Interventions	Patients were assessed monthly for response while on therapy, and interim restaging occurred at cycle 4. Those who achieved a complete response received no further therapy, whereas those who achieved a partial response or stable disease received 2 additional cycles Flu‐R: patients received fludarabine 25 mg/m2 IV on days 1 to 5 and rituximab 375 mg/m2 IV on days 1 and 4 of the first cycle. In the subsequent cycles they received additional rituximab 375 mg/m2 IV on day 1 Flu‐Cam: patients received fludarabine 25 mg/m2 IV and alemtuzumab 30 mg SC, on days 1 to 5 of each cycle
Outcomes	Outcomes relevant for this review: reported: CRR ORR AEs number of patients discontinuing the study because of drug‐related AEs not reported: OS PFS time to next treatment TRM MRD
Notes	No conflict of interest statement in the abstract
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "patients were randomized to" Comment: the authors did not describe the method used to generate the allocation sequence
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) Overall survival	Unclear risk	The study did not assess this outcome
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Comment: patient and physician unblinded. No information about blinding of outcome assessor provided
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: the information about completeness of outcome data is insufficient to permit judgement
Selective reporting (reporting bias)	High risk	Comment: the trial is published as abstracts Comment: protocol is registered (ClinicalTrials.gov: NCT00086775) Pre‐planned outcomes (relevant for the review) that were reported: CRR ORR AEs number of patients discontinuing the study because of drug‐related AEs Pre‐planned outcomes (relevant for the review) that were not reported: OS PFS MRD
Other bias	High risk	According to the protocol a total of 150 patients (75 per treatment arm) were needed for this study. The abstract reported the results of only 12 recruited patients Comment: the small number of 12 patients instead of 150 indicate that this are very preliminary results