CLL2007FMP.

Methods	Randomisation Two arms: 6 courses of fludarabine and cyclophosphamide (FluC) plus alemtuzumab (Cam) versus 6 courses of fludarabine and cyclophosphamide (FluC) plus rituximab (R) 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 (cumulative illness rating scale (CIRS) score < or = 6); creatinine clearance at least 60 ml/min No 17p deletion Patients randomised (N = 165) FluC‐Cam (N = 82): (withdrawals or exclusions not stated) FluC‐R (N = 83): (withdrawals or exclusions not stated) The trial was stopped early due to unacceptable toxicity in the FluC‐Cam arm (6 deaths versus 0 in FluC‐R arm) Mean age Not stated Gender (male, female) Not stated Stage of disease (Rai stage group) Not stated Countries France and Belgium
Interventions	FluC‐Cam (every 28 days; up to 6 cycles) Patients received fludarabine 40mg/m2 days 1 to 3 and cyclophosphamide 250 mg/m2 days 1 to 3 plus alemtuzumab 30 mg subcutaneous days 1 to 3 FluC‐R Patients received fludarabine 40mg/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 Anti‐infective prophylaxis included trimethoprim‐sulfamethoxazole and valaciclovir during immunochemotherapy and until the CD4‐positive lymphocyte count reached 0.2 109/L.
Outcomes	Primary outcome 36‐month PFS Secondary outcomes OS Disease‐free survival Event‐free survival Time to next treatment ORR (CRR and PR) Rate of phenotypic and molecular response Duration of phenotypic, molecular, complete and partial responses Response rates and survival times in biological subgroups Adverse effects Quality of life Minimal residual disease study Reported (relevant for this review) CRR ORR TRM MRD Adverse events Not reported (relevant for this review) OS PFS Time to next treatment Not evaluated (relevant for this review) Number of patients discontinuing the study because of drug‐related adverse events
Notes	The trial was discontinued after randomisation of 165 patients for unacceptable toxicity in the FluC‐Cam arm (6 deaths 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	Comment: The study did not report this outcome.
Blinding (performance bias and detection bias) All other 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: CR (FCR: 56/80 = 70%, FCCam: 45/79 = 59%, ns)" Reasons of exclusions are not provided.
Selective reporting (reporting bias)	High risk	Pre‐planned outcomes (ClinicalTrials.gov: NCT00564512) in the abstract‐publications reported for all pre‐defined outcomes except OS Disease‐free survival Event‐free survival PFS Time to next treatment Rate of phenotypic and molecular response Duration of phenotypic, molecular, complete and partial responses Response rates and survival times in biological subgroups Quality of life
Other bias	High risk	Quote: "The trial recruitment was discontinued because of an increase in mortality in the FCCam arm (6 deaths versus 0 in FCR arm), and the last 13 patients enrolled were not randomized" Comment: The trial was stopped early due to data‐dependent process.