|
| References | Regimen | No. | TLS % | TFR % | AE 3-4 (%) | Response |
|
Chanan Khan [31]
2006-7
Phase II
Relapsed or refractory | Lenalidomide 10 mg per day escalated up to 5 mg each 1-2 week (max 25 mg) 21 days each 28
Rituximab 375 mg/m2 days 1, 8, and 15 (cycle 1) and days 1 and 15 (cycles 2–6) | 30 | 5 | 8 | Neutropenia 70%
Thrombocytopenia 45%
Anemia 18% | ORR 57.7%
RC 18%
TFS 19.4 months
ORR 38% (high risk cytogenetic) |
|
James 2011 [30]
Phase II frontline
CLL Research Consortium CRC-014 | Lenalidomide cycle 1: 2.5 mg; cycles 2–7: 5 mg escalated up to 10 mg (days 1–21 each 28)
Rituximab: 50 mg/m2 day 29; 325 mg/m2 day 31; 375 mg/m2 day 33 (cycle 1), 375 mg/m2 weekly (cycle 2) and 375 mg/m2 day 1 (cycles 3–7) | 69 | | 1.4 | Neutropenia 49%
Thrombocytopenia 6%
Anemia 11% | ORR 95% (<65 y)
ORR 78% (>65 y)
RC 20% (<65 y)
RC 8% (>65 y)
TFS 19-20 m |
|
Badoux [29, 43]
Phase II relapsed or refractory | Lenalidomide was started on day 9 at cycle 1 and on day 1 of the cycles 3–12: 10 mg continuously
Rituximab 375 mg/m2 weekly during cycle 1 and on day 1 cycles 3 to 12 | 59 | 1.7 | 27 | Neutropenia 73%
Thrombocytopenia 34%
Anemia 15%
Infection 15% | ORR 66%
RC 12%
OS: 71% at 36 months
TFS: 17.4 m |
|
Veliz 2009 [32]
Phase II
Relapsed or progression after rituximab
Heavily treated | Lenalidomide cycle 1: 2.5 mg (days 1–7), 5 mg (days 8–15), 10 mg (15–21 days) followed by 7 days of rest and then 20 mg 21 each 28 days
Rituximab 375 mg/m2 weakly each 4 weeks (day 15) | 10 | (RF) 12 | 12 | Neutropenia 41% | ORR 30%
RC 0 |
|
Chen 2012 [39]
Phase II
frontline | Lenalidomide: 5 mg per day escalated 5 mg each 28 days (max 25 mg)
Dexamethasone: 12 mg days 1–4; 14, 21, and 28
Maximum 18 cycles | 18 | 0 | 5 | Neutropenia 53%
Neutropenia febrile 24%
Thrombocytopenia 12% | 0R 59%
RC 1%
RP 53% |
|
Badoux [33]
Phase II
Relapsed or refractory | Lenalidomide 10 mg per day
Ofatumumab weekly | 16 | NR | 13 | Neutropenia 50%
Anemia 13% | ORR 63%
RC: 13%
OS: NR
TFS: NR |
|
Ferrajoli [44]
2012
Phase II
Relapsed or refractory | Lenalidomide 10 mg day 9 continued for 24 months
Ofatumumab weekly for 3 weeks (300 mg week; 1000 mg week 2 and thereafter) monthly (months 2–6); every other month (months 7–24) | 36 | 0 | 0 | Neutropenia 47%
Thrombocytopenia 9%
Anemia 6% | ORR 68%
RC 24% |
|
Blum [38]
2011
Phase I
Relapsed or refractory very adverse | Lenalidomide 2.5 mg escalating up to 25 mg days 1–21
Flavopiridol 30 mg/m2 in bolus followed of 30–50 mg/m2 days 1, 8, and 15 (cycle 1) and then days 3, 10 and 17 | 30 | 3 | 7 | Neutropenia 47%
Thrombocytopenia 60%
Anemia 33% | ORR 57%
RC: 0%
OS 7 m
TFS 23 m |
|
GIMEMA [34]
LLC 606
Phase I
Relapsed or refractory | Lenalidomide 2.5 mg escalating up to 15 mg Cyclophosphamide Fludarabine | 9 | 0 | 11 | Neutropenia transitory 3-4 in the majority of the patients | ORR 67%
RC 33%
NR
NR |
|
Egle [36]
2011
Phase I/II
Frontline | Lenalidomide 2.5 mg/day (days 7–21) escalating up to 25 mg (day 1–21)
Fludarabine 40 mg/m2 1–3
Rituximab 375 m/m2 day 3 cycle 1; 500 mg/m2 day 1 cycles 2–6
Maintenance:
R: 375 mg/m2 cycles 2, 4, and 6 Lenalidomide (maximum tolerated dose) | 45 | 0 | 0 | Neutropenia 88% | ORR 87%
RC 49%
NR
NR |
|
Flinn [45]
2012
Phase I-II
Frontline | Rituximab 375 mg/m2 (cycle 1); 500 mg/m2 (cycle 2–6)
Fludarabine 25 mg/m2 (days 1–3)
Lenalidomide 2.5–5 mg (days 8–28)
6 cycles | 51 | 6 | 0 | Neutropenia 47%
Anemia 14%
Thrombocytopenia 6
Rash 14% | ORR: 78%
RC 19%
PFS 71%
OS 88%
(median FU 21 months) |
|
Brown [35]
Phase I
Frontline | Fludarabine: 25 mg/m2 (days 3–5)
Rituximab: 50 mg/m2 day 1 and 325 mg/m2 day 3
Lenalidomide: 2.5 mg to alternate days (21 each 28 days)
Followed by two cycles of consolidation with lenalidomide | 9 | 1/9 | 2/9 | Neutropenia 66%
Thrombocytopenia 2/9
Allergy
Syndrome hand-foot | ORR 56%
RC 1/9 |
|
