Study design
The ECOG 1912 study was an open-label, randomised, phase III study comparing the treatment regimens fludarabine, cyclophosphamide, and rituximab (FCR) and IMBRUVICA® and rituximab (IMBRUVICA® + R), in firstline CLL patients ≤70 years old who required therapy.[1][2]
Median age[1]
All patients
58 years
Key patient eligibility criteria:[1][2]
- Treatment-naïve CLL/SLL requiring therapy
- ≤70 years
- ECOG PS 0–2
- Del(17p) exclusion
The ECOG 1912 study included patients with high-risk features[1]
High-risk features included del(11q), and uIGHV
Baseline characteristics[1]*
Characteristic | IMBRUVICA® + R | FCR | Total |
| Mean age ≥60 years, n (%) | 56.7±7.5 | 56.7±7.2 | 56.7±7.4 |
| Female, n (%) Male, n (%) | 118 (33.3) | 55 (31.4) | 173 (32.7) |
| Rai stage, n (%) Low risk, 0 Intermediate risk, I or II High risk, III or IV | 11 (3.1) 187 (52.8) 156 (44.1) | 9 (5.1) 94 (53.7) 72 (41.1) | 20 (3.8) |
ECOG performance- status score, n(%)† |
|
| 335 (63.3) |
β-2 microglobulin level, mg/L |
|
|
|
Döhner classification, n (%) |
|
| 2 (0.4) |
IGHV mutation status, n/total n (%)§ |
|
| 114/395 (28.9) |
7 x 28-day cycles of:[1][2]
Rituximab
50 mg/m2 on Day 1 of cycle 2
325 mg/m2 on Day 2 of cycle 2
500 mg/m2 on Day 1 of cycles 3–7
(n=354)
and
IMBRUVICA®420 mg once daily
until disease progression or unacceptable toxicity[1]
6 x 28-day cycles of:[2]
Fludarabine
25 mg/m2 Days 1–3
Cyclophosphamide
250 mg/m2 Days 1–3
Rituximab
50 mg/m2 on Day 1 of cycle 1
325 mg/m2 on Day 2 of cycle 1
500 mg/m2 on Day 1 of cycles 2–6
(n=175)[1]
Primary endpoint[1][2]
PFS
Secondary endpoint[1][2]
OS
45.0 months extended median follow-up[2]
CLL patient subgroups
uIGHV patients
Genetic aberration patients
Fit patients
Relapsed / refractory patients
Back to IMBRUVICA® studies
*Plus–minus values are means ±SD. Patients were randomly assigned to receive IR or CIT with FCR. Data include patients with SLL; overall, 11.4% of the patients (11.7% in the IR group and 10.9% in the CIT group) had the SLL subtype of CLL. Percentages may not total 100 because of rounding.[1]
†ECOG performance status scores are assessed on a 5-point scale, with higher scores indicating greater disability.[1]
‡Two patients with chromosome 17p13 deletion were enrolled and randomly assigned to the IR group but were later found to be ineligible on the basis of FISH analysis.[1]
§IGHV mutation status was tested in the 436 patients (82.4% of the overall population) who agreed to participate in the correlative study component of the trial and who provided a research sample. Among the 436 patients who underwent testing, IGHV status could be determined in 395.[1]
CIT=chemoimmunotherapy; CLL=chronic lymphocytic leukaemia; ECOG PS=Eastern Cooperative Oncology Group Performance Status; FCR= fludarabine + cyclophosphamide + rituximab; FISH=fluorescence in situ hybridisation; IGHV=immunoglobulin heavy-chain variable region; OS=overall survival; PFS=progression-free survival; R=rituximab; R/R= relapsed/refractory; SLL=small lymphocytic lymphoma; SD=standard deviation; uIGHV=unmutated immunoglobulin heavy-chain variable region.
