CLL2007FMP

Methods	Randomisation: 2 arms: 6 courses of FluC‐‐R versus 6 courses of FluC‐Cam Recruitment period: November 2007 to January 2009 Median follow‐up time: not stated
Participants	Eligibility criteria: previously untreated B‐cell CLL Binet classification stages B or C younger than 65 years medically fit patients (CIRS score ≤ 6); creatinine clearance at least 60 mL/min no 17p‐deletion Patients randomised (N = 165): FluC‐R (N = 83): withdrawals or exclusions not stated FluC‐Cam (N = 82): withdrawals or exclusions not stated The trial was stopped early owing to unacceptable toxicity in the FluC‐Cam arm (6 deaths in FluC‐Cam arm versus 0 in FluC‐R arm) Mean age: not stated Gender (male, female): not stated Stage of disease (Rai stage group): not stated Countries: French and Belgium
Interventions	FluC‐R: patients received fludarabine 40 mg/m2 days 1 to 3 and cyclophosphamide 250 mg/m2 days 1 to 3 plus 375 mg/m2 rituximab IV day 0 at first cycle and 500 mg/m2 day 1 all subsequent cycles FluC‐Cam (every 28 days; up to 6 cycles): patients received fludarabine 40 mg/m2 days 1 to 3 and cyclophosphamide 250 mg/m2 days 1 to 3 plus alemtuzumab 30 mg SC days 1 to 3 Anti‐infective prophylaxis included trimethoprim‐sulfamethoxazole and valacyclovir during immunochemotherapy and until the CD4‐positive lymphocyte count reached 0.2 × 109/L
Outcomes	Outcomes and time points from the study that were considered in the review: reported: CRR ORR TRM MRD AEs not reported: OS PFS time to next treatment number of patients discontinuing the study because of drug‐related AEs
Notes	The trial was discontinued after randomisation of 165 patients for unacceptable toxicity in the FluC‐Cam arm (6 deaths in FluC‐Cam arm versus 0 in FluC‐R arm). The last 13 patients enrolled were not randomised The authors stated that they had no relevant conflict of interest to declare
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	Quote: "165 patients were randomized to (...) R (N = 83 (...)) or Cam (N = 82)"; "Clinical responses were as follows: CRR (FCR [FluC‐R]: 56/80 = 70%, FCCam: 45/79 = 59%, ns)" Reasons of exclusions are not provided
Selective reporting (reporting bias)	High risk	Comment: the trial is published as abstracts Comment: protocol is registered (ClinicalTrials.gov: NCT00564512) Pre‐planned outcomes (relevant for the review) that were reported: CRR ORR TRM MRD AEs Pre‐planned outcomes (relevant for the review) that were not reported: OS PFS time to next treatment number of patients discontinuing the study because of drug‐related AEs
Other bias	High risk	Quote: "the trial recruitment was discontinued because of an excess of mortality in the FCCam arm (6 deaths versus 0 in FluC‐R arm), and the last 13 patients enrolled were not randomized" Comment: the trial was stopped early owing to data‐dependent process