Table 1.
Characteristics of the Patients at Baseline.*
| Characteristic | Dose-Escalation Cohort (N = 56) | Expansion Cohort (N = 60) | All Patients (N = 116) |
|---|---|---|---|
| Age | |||
| Median (range) — yr | 67 (36–86) | 66 (42–84) | 66 (36–86) |
| ≥70 yr — no. (%) | 20 (36) | 14 (23) | 34 (29) |
| Sex — no. (%) | |||
| Male | 41 (73) | 48 (80) | 89 (77) |
| Female | 15 (27) | 12 (20) | 27 (23) |
| Diagnosis — no. (%) | |||
| Chronic lymphocytic leukemia | 49 (88) | 53 (88) | 102 (88) |
| Small lymphocytic lymphoma | 7 (12) | 7 (12) | 14 (12) |
| Rai stage III or IV — no. (%) | 28 (50) | 39 (65) | 67 (58) |
| Median no. of previous therapies (range)† | 4 (1–10) | 3 (1–11) | 3 (1–11) |
| Resistance to most recent therapy — no. (%)‡ | 23 (41) | 22 (37) | 45 (39) |
| Previous fludarabine-based therapy — no. (%) | |||
| Any previous fludarabine | 51 (91) | 49 (82) | 100 (86) |
| Resistance to fludarabine | 28 (50) | 42 (70) | 70 (60) |
| ECOG performance status — no. (%) | |||
| Grade 0 | 29 (52) | 27 (45) | 56 (48) |
| Grade 1 | 27 (48) | 31 (52) | 58 (50) |
| Missing data | 0 | 2 (3) | 2 (2) |
| Peripheral-blood lymphocytosis | |||
| Absolute lymphocyte count >5000 per mm3 — no. (%) | 31 (55) | 35 (58) | 66 (57) |
| Median count per mm3 (range) | 27,600 (5400–204,500) | 25,100 (5200–259,900) | 27,500 (5200–259,900) |
| Bulky nodes — no. (%) | |||
| >5 cm | 29 (52) | 38 (63) | 67 (58) |
| >10 cm | 10 (18) | 12 (20) | 22 (19) |
| Interphase cytogenetic abnormality — no./total no. with CLL (%)§ | |||
| Chromosome 17p deletion | 19/49 (39) | 12/53 (23) | 31/102 (30) |
| Chromosome 11q deletion | 13/49 (27) | 15/53 (28) | 28/102 (27) |
| No chromosome 17p or 11q deletion | 16/49 (33) | 27/53 (51) | 43/102 (42) |
| Data missing or indeterminate | 7/49 (14) | 3/53 (6) | 10/102 (10) |
| IGHV mutation status — no./total no. with CLL (%) | |||
| Unmutated | 26/49 (53) | 20/53 (38) | 46/102 (45) |
| Mutated | 6/49 (12) | 11/53 (21) | 17/102 (17) |
| Data missing | 17/49 (35) | 22/53 (42) | 39/102 (38) |
*
ECOG denotes Eastern Cooperative Oncology Group, and IGHV immunoglobulin heavy-chain variable region.
†
A total of 116 patients (100%) received anti-CD20 antibodies, 110 (95%) received alkylating agents, and 103 (89%) received purine analogues.
‡
Resistance was defined as either a lack of at least a partial response or disease progression while receiving therapy or within 6 months after the completion of therapy. Nineteen patients with resistance to fludarabine were also resistant to the combination of fludarabine, cyclophosphamide, and rituximab.
§
A total of 11 patients — 7 in the dose-escalation cohort and 4 in the expansion cohort — had both chromosome 17p and chromosome 11q deletions.