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S. Bringhen et al.
Table 2. Data from clinical trials of carfilzomib in relapsed/refractory multiple myeloma and newly diagnosed multiple myeloma.
Study Phase
Relapsed and refractory MM
ASPIRE37 3
ENDEAVOR31 3
FOCUS40 3
PX-171-003-007-A038 2 PX-171-003-007-A138 2 PX-171-00438 2 PX-171-00538 2
CHAMPION-141 1-2 Phase 1
Phase 2
Newly diagnosed MM
CLARION47,48 3
MYELOMA XI60
CHAMPION-249 1b
N. of patients
396 396
464 465
157
158
46 266 164 50
116 27
89
478 477
526
1021 1021
3 (36 mg/m2) 3 (45mg/m2) 16 (56mg/m2)
Regimen
CFZ20mg/m2 cycle1d1+2,27mg/m2 ond8,9,15,16 cycle 2+ 27 mg/m2 on d 1, 2, 8, 9, 15, 16 R25mgd1–21,D40mg ond1,8,15,22 R25mgdays1–21,D40mg ond1,8,15,22
CFZ20mg/m2 cycle1d1+2,56mg/m2 ond8,9,15,16 cycle2+56mg/m2 ond1,2,8,9,15,16
D20mg ond1,2,8,9,15,16,22,23
V1.3mg/m2 ond1,4,8,11,D20mg ond1,2,4,5,8, 9, 11, 12
Median prior lines (range)
2(1–3) 2(1–3)
2(1–2) 2(1–2)
Notes
≈50% of patients received a prior ASCT
with Mel200
≈60% previously received V, 20% lenalidomide
Prior antimyeloma drugs, median (range) 8 (5–17)
Prior antimyeloma drugs, median (range) 8.5 (4–14)
Median CFZ treatment duration 7.8 months
Each regimen was given as 42-day treatment
Patients were planned to receive a minimum of 4 cycles of induction. Therapy was continued to maximum response or intolerance. After induction eligible patients could undergo autologous transplant.
Treatment was continued for 8 cycles or until unacceptable toxicity, withdrawal of consent, or progressive disease.
After completing 9 cycles, patients received maintenance with CFZ until progression or intolerance.
Median age: 72 (range: 55-85) years, 38 (26%) patients were >75 years old. Median follow-up was 21 months.
CFZ20mg/m2 cycle1d1+2,27mg/m2 ond8,9,15,16 5(3–15) cycle 2-9 27 mg/m2 on d 1, 2, 8, 9, 15, 16
cycle 10+ 27 mg/m2 on d 1, 2, 15, 16; treatment on d 8
and 9 was optional per the investigator’s discretion
P 30 mg or D 6 mg or other equivalent corticosteroid (not to exceed 84 mg D or equivalent per 28-d cycle). Patients could receive optional V 50 mg per the investigator’s discretion.
CFZ 20 mg/m2 on d 1, 2, 8, 9, 15, 16; 28-d cycles
CFZ 20/27 mg/m2 on d 1, 2, 8, 9, 15, 16; 28-d cycles CFZ20or27mg/m2 ond1,2,8,9,15,16;28-dcycles CFZ15,20or27mg/m2 ond1,2,8,9,15,16;28-dcycles
5 (3–17)
4 4 4 4
CFZ on d 1, 8, and 15 of 28-d cycles. 20 mg/m2 on
cycle 1, d 1 (C1D1); subsequent doses (beginning with
C1D8) escalated at 45, 56, 70, or 88 mg/m2 to determine MTD CFZ at MTD according to the same schedule as phase 1. 1 D40mgd1,8,15,22ofa28-dcycleforthefirst8cycles
and omitted on d 22 during cycle 9 and beyond.
Median n of cycles
CFZ 20 mg/m2 d 1-2 and 36 mg/m2 thereafter
M 9 mg/m2 and P 60 mg/m2 d 1-4 of each treatment
cycle for 9 cycles
BTZ1.3mg/m2 ond1,4,8,11,22,25,29,32
M 9 mg/m2 and P 60 mg/m2 d 1-4 of each treatment cycle 9
1
9
NCT0220424150 1-2 148 NCT0185711550
NCT0134678750
CFZ 20 mg/m2 d 1-2 and 36 mg/m2 thereafter Cy500mg/m2 ond1,8
R 25mg/d, d 1-21, D weekly (40/20mg cycles 1-4/5+) in 28-d cycles
Cy 500 mg/m2 on d 1, 8
R 25 mg/d, d 1-21, D weekly (40/20 mg cycles 1-4/5+)
in 28-d cycles
Cy500mg/m2 ond1,8,15
T 100-200 mg/d, d 1-21, D weekly (40/20 mg cycles 1-4/5+) in 28-d cycles
CFZ, twice-weekly, 3 + 3 dose escalation at 36, 45, and 56 mg/m2, followed by dose expansion.
CFZond1,2,8,9,15,16ofeachcycle(20mg/m2 on d 1 + 2 of cycle 1 and the escalated dose thereafter), Cy300mg/m2 ond1,8,15
D on d 1, 8, 15, 22 of each 28-day cycle.
CFZ 36 mg/m2 on d 1, 2, 8, 9, 15, 16 in NCT02204241,
3 dose levels escalated from 45-70 mg/m2 on d 1, 8, 15 in NCT01857115, and on d 1, 2, 8, 9, 15, 16 in NCT01346787. Cy300mg/m2 ond1,8,15,D40mg1x/week
8
9
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haematologica | 2018; 103(9)