Table 3.
Trials of combination regimens, primarily in relapsed/refractory chronic lymphocytic leukemia (CLL), with at least 20 patients enrolled.
| Trial | Regimen (route) | No. enrolled | Median prior lines (range) | ORR, % (CR, %) | Median OS, months | Median PFS, months | Patient characteristics |
|---|---|---|---|---|---|---|---|
| Faderl et al. [2003] | A (IV) + R (IV) | 48 (32 CLL, 9 CLL/PLL) | 4 (1–9) | 52 (8) | 11 | 6 | r/r |
| Elter et al. [2005] | A (IV) + F (nr) | 36 | 2 (1–8) | 83 (31) | 35.6 | 13 | r/r |
| Flowers et al. [2007] | A (SC) + F (IV) | 28 | 3 (1–14) | 64 (21) | nr | nr | r/r |
| Brown et al. [2010] | A (SC) + R (IV) | 28 | 4 (1–11) | 64 (14) | 47 | 13 | r/r |
| Faderl et al. [2010] | A (IV) → A (SC) + R (IV) | 40 | 3 (1–8) | 53 (18) | nr | 6 | r/r |
| Stilgenbauer et al. [2010] (CLL2O) | A (SC) + Dex (PO) → A (SC) or allogeneic SCT (patient preference) | 50 | 2 (1–5 17p- relapse, 1–6 F r/r) | 47 (0) F r/r; 78 (0) 17p- relapse | nr | nr | Fludarabine r/r (N = 19); 17p- untreated (N = 22); 17p- relapsed (N = 9) |
| Badoux et al. [2011] | A (IV) + F (IV) + Cy (IV) + R (IV) | 80 | 3 (1–14) | 65 (29) | 16.7 | 10.6 | r/r |
| Elter et al. [2011] * | A (IV) + F (IV) versus F (IV) | 335 | nr | 82 (13) versus 75 (4) (p = NS) | Not reached versus 52.9 (p = 0.02) | 23.7 versus 16.5 (p = 0.0003) | r/r |
| Montillo et al. [2011] | A (SC) + F (PO) + Cy (PO) | 43$ | 2 (1–4) | 67 (30) | 33.6 | 24.4 | r/r |
| Tedeschi et al. [2011] | A (SC) + B (IV) | 29 | 2 (1–6) | 61 (26) | nr | nr | r/r |
| Elter et al. [2012] (CLL2L) | A (SC) + F (IV) + Cy (IV) | 61 | 1 (0–4) | 56 (11) | 45 | 17 | r/r (N = 56); high risk untreated (N = 5) |
| Pettitt et al. [2012] (CLL206) | A (IV) →A (SC) + methylprednisolone (nr) | 39 | nr (1–4) | 77 (14) | 23 (all) | 6.5 (r/r) | TP53 deleted (all); r/r (N = 22); untreated (N = 17) |
| Total number Treated | 817 |
Unless otherwise noted, all patients had CLL.
A, alemtuzumab; B, bendamustine; CR, complete response; Cy, cyclophosphamide; Dex, dexamethasone; F, fludarabine; IV, intravenous; nr, not reported; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PLL, prolymphocytic leukemia; PO, oral; R, rituximab; r/r, relapsed/refractory; SC, subcutaneous.
*
Phase III randomized trial.
$
46% 17p- or 11q-.