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.
Median age
All patients
58 years
Key patient eligibility criteria:
- 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
High-risk features included del(11q), and uIGHV
Baseline characteristics*
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:
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
6 x 28-day cycles of:
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)
Primary endpoint
PFS
Secondary endpoint
OS
45.0 months extended median follow-up
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.
†ECOG performance status scores are assessed on a 5-point scale, with higher scores indicating greater disability.
‡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.
§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.
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.
