Table 5.
Results of clinical trials on B-CLL with fludarabine and monoclonal antibody
| References | Comp study | No of evaluable pts | Prior therapy | Treatment regimen | Clinical response
|
Survival/duration of response | |
|---|---|---|---|---|---|---|---|
| CR (%) | OR (%) | ||||||
| Byrd et al79 | yes | 104 | no | FAMP 25 mg/m2 iv d1–5 q 4 wk × 6 cycles followed by R 375 mg/m2/w iv × 4 doses (n, 53) | 47 | 90 | PFS 28%, OS 96% at 23 mo |
| FAMP 25 mg/m2 iv d1–5 + R 375 mg/m2 iv d1 followed by R 375 mg/m2/wk iv × 4 doses (n, 51) | 28 | 77 | PFS 35%, OS 88% at 23 mo | ||||
| Byrd et al82 | yes | 282 | no | FAMP 25 mg/m2 iv d1–5 q 4 wk+/–
R 375 mg/m2 iv × 6 cycles followed by R 375 mg/m2/w iv × 4 doses (n,104) |
38 | 84 | PFS 67%, OS 93% at 2 yrs |
| FAMP 25 mg/m2 iv × d1–5 q 4 wk (n, 179) | 20 | 63 | PFS 45%, OS 81% at 2 yrs | ||||
| Wierda et al80 | no | 177 | yes | FAMP 25 mg/m2 iv d1/2–3/4 + CTX 250 mg/m2 iv d1/2–3/4 + R 375–500 mg/m2 iv d1 q 4 wk |
25 | 73 | 28 mo median PFS |
| Keating et al81 | no | 224 | no | FAMP 25 mg/m2 iv d1/2–3/4+CTX 250 mg/m2 iv d1/2–3/4 +R 375–500 mg/m2 iv d1 q 4 wk |
70 | 95 | TTF 69% at 4 yrs |
| Hallek et al85 | yes | 761 (for resp.) | no | FAMP 25 mg/m2 iv d1/2–3/4+CTX 250 mg/m2 | 52 | 95 | PFS 76.6% and OS 91% at 2 yrs PFS |
| 787 (for PFS) | iv d1/2–3/4 +R 375–500 mg/m2 iv d1 q 4 wk | 27 | 88 | 62.3% and OS 88% at 2 yrs | |||
| 871 (for OS) | FAMP 25 mg/m2 iv d1/2–3/4 +CTX 250 mg/m2 iv d1/2–3/4 | ||||||
| Foon et al86 | no | 48 | no | FAMP 20 mg/m2 d1–3+CTX 150 mg/m2 d1–3 +R-500 mg/m2 d1 and d14 q 4 wk; maintenance R-500 mg/m2 q3 mo until progression |
79 | 100 | 22.3 mo median PFS |
| Bosch et al88 | no | 72 | no | FAMP 25 mg/m2 iv d1/2–3/4 +CTX 250 mg/m2 iv d1/2–3/4+MIT 6 mg/m2 iv d 1 +R 375–500 mg/m2 iv d1 q 4 wk |
82 | 93 | na |
| Tsimberidou et al87 | no | 50 (30 B-CLL20 RS) | yes | O 17.5, 20, or 25 mg/m2 iv d1–4+FAMP 30 mg/m2 iv d2–3+ ara-C 1 g/m2 iv d2–3+R 375 mg/m2 d1 or d3 q 4 wk | 0 (B-CLL)
10 (RS) |
36 (B-CLL)
50 (RS) |
TTF 47%, OS 89% at 6 mo (B-CLL)
TTF 54%, OS 59% at 6 mo (RS) |
| Kennedy et al93 | no | 6 | yes | FAMP dose not applicable A dose not applicable | 17 | 83 | na |
| Elter et al94 | no | 36 | yes | A 30 mg iv+FAMP 30 mg/m2 iv d1–3 q 4 wk | 31 | 83 | 35.6 mo median OS
12.9 mo median PFS |
| Wierda et al96 | no | 21 | no | CTX 200 mg/m2 d3–5+FAMP 20 mg/m2 d3–5 A 30 mg
iv d1, 3, 5 R 375–500 mg/m2 d2 q 4 wk |
71 | 95 | na |
| Montillo et al97 | no | 19 | yes | FAMP 40 mg/m2 os d1–3+CTX 250/m2 os d1–3+A 10–20 mg sc d1–3 |
37 | 79 | na |
| Elter et al98 | no | 20 | yes | FAMP 25 mg/m2 iv d1–3 +CTX 200 mg/m2 iv d1–3+A 30 mg sc d1–3 |
25 | 70 | na |
| Byrd et al99 | yes | 31 | yes | Lu 375–500 mg/m2 +FAMP 25 mg/m2 iv d1/2–3/4+
CTX 250 mg/m2 iv d1/2–3/4 +R 375–500 mg/m2 iv d1 q 4 wk. Comparison with FCR Wierda et al 2005 |
48 | 71 | na |
Abbreviations: Comp, comparative; RS, Richter’s syndrome; resp., response; CR, complete remission; OR, overall response; OS, overall survival; PFS, progression-free survival; TTF, time to treatment failure; FAMP, fludarabine; MIT, mitoxantrone; ara-C, cytarabine; R, Riuximab; O, oxaliplatin; A, alemtuzumab; Lu, lumiliximab; d, days; mo, months; wk, weeks; q, every; iv, intravenous; os, oral; sc, subcutaneous; pts, patients; na, not applicable.