Table 3.
Phase I/II and III trials of idelalisib ± anti-CD20 monoclonal antibodies
| Study | Cohort | ORR/CRR MRD | PFS/OS | III/IV toxicity (> 10%) |
|---|---|---|---|---|
| Phase I/II | ||||
| Brown et al.[191]
NCT00710528 NCT01090414 (idelalisib monotherapy) |
R/R CLL
(n = 54) |
72%/0% | Median PFS 16 months
75% OS at 3 years |
Neutropenia 43%
Pneumonia 20% Neutropenic fever 11% |
| Furman et al.[194,195]
(idelalisib + rituximab% or ofatumumab^) |
R/R CLL
(n = 40) |
83%/5% | Median PFS 24 months
80% OS at 24 months |
Diarrhea/colitis 23%
Pneumonia 18% |
| O’Brien et al.[200]
NCT01203930 (idelalisib-rituximab%) |
TN ≥ 65 years
(n = 64) |
97%/19% | PFS 83% at 3 years
OS 90% at 3 years |
Diarrhea/colitis 42%
Neutropenia 28% ALT/AST elevation 23% Pneumonia 19% |
| Zelenetz et al.[193]
(idelalisib monotherapy) |
TN ≥ 65 years
(n = 37) |
81%/0% | NA | Neutropenia 20% |
| Lampson et al.[201]
NCT02135133 (idelalisib-ofatumumab^) |
TN
(n = 27) |
89%/4% | Median PFS 23 months
OS 88% at 3 years |
ALT/AST elevation 52%
Neutropenia 33% Colitis/diarrhea 15% |
| Phase III | ||||
| Coutre et al.[202]
NCT01088048 (idelalisib ± rituximab% ± bendamustine) |
R/R CLL
IDEL + R (n = 19) |
90%/0% | Median PFS 37 months | Neutropenia 26%
Pneumonia 21% Diarrhea 16% Febrile neutropenia 16% |
| IDEL + BEN (n = 18) | 78%/6% | Median PFS 19 months | Neutropenia 67%
Thrombocytopenia 22% Anemia 28% AST/ALT elevation 22% Pneumonia 22% Sepsis 22% Febrile neutropenia 17% |
|
| IDEL + BEN + R (n = 15) | 88%/13% | Median PFS 23 months | Neutropenia 60%
Anemia 13% Diarrhea 13% Pneumonia 13% Rash 13% |
|
| Furman et al.[16,203]
NCT01539512 (idelalisib-rituximab# vs. rituximab monotherapy#) |
R/R CLL with: myelosuppression, CrCl < 60 mL/min or CIRS > 6
IDEL + R (n = 110) |
81%/0% | 66% PFS at 12 months
92% OS at 12 months |
Neutropenia 34%
Thrombocytopenia 10% |
| R (n = 110) | 13%/0% | 13% PFS at 12 months
80% OS at 12 months |
Neutropenia 22%
Thrombocytopenia 16% Anemia 14% |
|
| Jones et al.[204,205]
NCT01659021 (idelalisib-ofatumumab^ vs. ofatumumab monotherapy*) |
R/R CLL
IDEL + OFA (n = 174) |
75%/0% | Median PFS 16 months
Median OS NR |
Neutropenia 34%
Diarrhea 23% Pneumonia 20% |
| OFA (n = 87) | 18%/0% | Median PFS 8 months
Median OS NR |
Neutropenia 16% | |
Idelalisib (IDEL) used as continuous therapy until progression, death, or other reason to withdraw in all trials. %375 mg/m2 weekly for 6-8 weeks; #375 mg/m2 for first dose, 500 mg/m2 every two weeks for four doses, then 500 mg/m2 every four weeks for three doses (total eight doses). OFA^: ofatumumab intravenously 300 mg Week 1, 1000 mg Weeks 2-7, 1000 mg Q4 weekly × 4; OFA*: ofatumumab intravenously 300 mg Week 1, 2000 mg Weeks 2-7, 2000 mg Q4 weekly × 4. ORR: overall response rate; CRR: complete response rate; PFS: progression free survival; OS: overall survival; R/R: relapsed and refractory; TN: treatment naïve; R: rituximab; BEN: bendamustine; CIRS: cumulative illness rating scale; CrCl: creatinine clearance; PB uMRD: peripheral blood measurable residual disease less than 10-4; BM uMRD: bone marrow measurable residual disease less than 10-4