GCLLSG CLL4B.

Methods	Randomisation Two arms: up to 12 weeks alemtuzumab consolidation therapy versus observation Recruitment period Not stated Median follow‐up time 48 months from start of chemotherapy with Flu or FluC (range not stated).
Participants	Eligibility criteria B‐cell CLL in first complete or partial remission after fludarabine or fludarabine/cyclophosphamide first‐line therapy Between 18 and 66 years of age Alemtuzumab had to be started no less than 30 days and no more than 90 days after the last dose of fludarabine or fludarabine/cyclophosphamide No autoimmune cytopenia or severe infections during first line treatment; no medical conditions requiring long‐term use of oral corticosteroids Patients recruited (N = 23) Two patients refused initiation of study treatment after randomisation and were excluded from analysis Alemtuzumab (N = 11): (withdrawals or exclusions not stated) Observation (N = 10): (withdrawals or exclusions not stated) Mean age Alemtuzumab: 60 years (range 38 to 63 years); observation: 58 years (range 37 to 66 years) Gender (male) Alemtuzumab: 8 (72.7%); observation: 7 (70.0%) Stage of disease (according to Rai) Alemtuzumab: 1 Rai I, 10 Rai II; observation: 1 Rai I, 6 Rai II, 1 Rai III; 2 Rai IV Countries Germany and Austria
Interventions	Patients received six cycles of fludarabine (25 mg/m2 days 1 to 5 IV every 28 days) or fludarabine/cyclophosphamide (fludarabine 30 mg/m2 d1 to 3 IV, cyclophosphamide 250 mg/m2 days 1 to 3 IV every 28 days). Patients were stratified according to induction treatment and response to induction treatment and randomised for treatment with alemtuzumab or observation. Alemtuzumab Patients received 3 mg on day 1; if well tolerated, dose was increased to 10 mg on day 2 and to the target dose of 30 mg on day 3. The 30 mg dose was subsequently given three times per week as a 2‐h infusion for a maximum of 12 weeks. Therapy was discontinued, if an unacceptable toxicity occurred and stopping criteria for the trial were set as grade 3 or 4 infections occurring in the alemtuzumab arm in five of the first 10 patients. Premedication with antihistamines (e.g., 2 mg IV clemastin), paracetamol (500 mg PO) and prednisone (100 mg IV) was given with the first dose at each escalation and thereafter only if clinically indicated. Anti‐infective prophylaxis including cotrimoxazole (960 mg PO twice daily, three times per week) and famciclovir (250 mg PO, twice daily) was given during and up to a minimum of 2 months following the discontinuation of alemtuzumab therapy. Control No further treatment
Outcomes	Reported Primary outcome PFS Secondary outcomes OS Time to next treatment TRM CRR ORR MRD Adverse events Number of patients discontinuing the study because of drug‐related adverse events Not reported None
Notes	The study was supported by a research grant of Schering AG, Berlin and MedacSchering Onkologie, Germany
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	High risk	Quote: "In all, 23 patients were recruited for this study, two patients refused initiation of study treatment after randomisation and were excluded from analysis." Comment: It is unclear in which group the two patients (8.7%) were randomised, why they refused treatment according to randomisation and why they were not analysed as randomised.
Selective reporting (reporting bias)	Unclear risk	Comment: The study has no registered study protocol. The review authors have not information to permit judgement.
Other bias	High risk	Quote: "This randomized phase III trial shows that a consolidation with alemtuzumab in a standard dose of 30mg IV TIW in CLL patients responding to fludarabine‐based chemotherapy is associated with an increased incidence of severe infections and myelotoxicity. Therefore, this multicenter trial was prematurely closed."