Table 1.

Select clinical trials evaluating rituximab containing chemoimmunotherapy combinations for the initial treatment of chronic lymphocytic leukemia.^18–29

Number of patients	Median age (years)	Chemotherapy* (mg/m2)	Rituximab schedule (mg/m2)	Cumulative rituximab dose (mg/m2)	Overall response rate† (%)	Complete response rate† (%)	Progression free survival (median)	Reference
104 Sequential arm: n = 53	63	Fludarabine 25 d 1–5×6 cycles	2 months following initial 6 cycles, Rituximab 375 weekly for 4 weeks	1500	77	28	40 mo	Byrd18–19
Concurrent arm: n = 51	63	Fludarabine 25 d 1–5×6 cycles	Rituximab 375 d 1 & 4 cycle 1 and d	4125	90	47	32 mo
			1 cycle 2–6 then
			2 months following initial 6 cycles, Rituximab 375 weekly for 4 weeks
300	58	Fludarabine 25 d 2–4 cycle 1, d 1 −3 cycles 2–6	Rituximab 375 d 1 cycle 1 and 500 d 1 cycle 2–6	2875	95	70	57% at 6 years	Keating20–21
		Cyclophosphamide 250 d 2–4 cycle 1, d 1–3 cycles 2–6
817 FC arm: n = 409	61	Fludarabine 25 d 1–3×6 cycles	None	0	85	23	32 mo	Hallek22
		Cyclophosphamide 250 d 1–3°—6 cycles
FCR arm: n = 408	61	FCR (same as FC arm)	Rituximab 375 cycle 1 d 0 and 500 on d 1 cycle 2–6	2875	93	45	43 mo
64	63	Pentostatin 2 d 1 q 3 weeks × 6 cycles	Rituximab 100 d 1, 375 d 3 and 5 cycle 1 and 375 d 1 cycle 2–6	2725	91	41	33 mo	Kay23
		Cyclophosphamide 600 d 1 q 3 weeks × 6 cycles (cycles administered every 21 days)
50	58	Fludarabine 20 d 2–4 cycle 1, d 1 −3 cycles 2–6	Rituximab 375 d 1 cycle 1 and 500 d 14 cycle 1, d 1 and 14 cycle 2–6 & Rituximab 500 every 3 mo until relapse	5875+500 every 3 mo until relapse	100	79	Response duration 22 mo	Foon24
		Cyclophosphamide 150 d 2–4 cycle 1, d 1–3 cycles 2–6
36	59	Fludarabine 25 d 1–5×6 cycles then Cyclophosphamide 3000 every 3 wks × 3 cycles	Following 9 cycles of sequential FC, Rituximab consolidation 375 weekly for 4 weeks	1500	89	61	43 mo	Lamanna25
30	57	Fludarabine 25 d 2–4 cycle 1, d 1 −3 cycles 2–6	Rituximab 375 d 1 cycle 1 and 500 d 1 cycle 2–6	2875	96	83	Not reached at 39 mo	Faded27
		Cyclophosphamide 250 d 2–4 cycle 1, d 1–3 cycles 2–6
		Mitoxantrone 6 d 2 cycle 1, d 1 cycles 2–6
72	60	Fludarabine 25 d 1–3×6 cycles	Rituximab 375 d 1 cycle 1 and 500 d	5875	93	82	Not reported	Bosch26
		Cyclophosphamide 250 d 1–3×6	1 cycle 2–6, responders receive 375 q
		cycles Mitoxantrone 6 d 1 × 6 cycles	3 months for 2 years
117	64	Bendamustine 90 d 1–2×6 cycles	Rituximab 375 d 1 cycle 1 and 500 d 1 cycle 2–6	2875	91	33	76% at 18 mo, median not reached	Fischer28
60	59	Cyclophosphamide 200 d 3–5×6 cycles	Rituximab 375 d 2 cycle 1 and 500 d 2 cycle 2- 6	2875	92	72	38 mo	Parikh29
		Fludarabine 20 d 3–5×6 cycles
		Alemtuzumab 30 mg flat dose d 1, 3, 5×6 cycles

^*Cycles are 28 days unless otherwise noted.

^†All responses were assessed by National Cancer Institute-working group (NCI-WG) 1996 criteria.

CFAR=FCR and alemtuzumab; CR=complete response; d=days; FC=fludarabine and cyclophosphamide; FR=fludarabine and rituximab; FCR=FC and rituximab; FCM-R=FCR and mitoxantrone; mo=months; PFS=progression-free survival; PCR=pentostatin, cyclophosphamide, and rituxumab; pt(s)=patients; RD=response duration.