Idelalisib and rituximab in relapsed chronic lymphocytic leukemia: trial

Idelalisib and rituximab in relapsed chronic lymphocytic leukemia

Population

Relapsed CLL with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses (patients less able to undergo standard chemotherapy)

Design

Multicentre, randomised, double-blind, placebo-controlled phase 3 study; 220 patients randomly assigned to rituximab plus idelalisib 150 mg twice daily or rituximab plus placebo. Primary endpoint PFS. At the first prespecified interim analysis the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy.

Primary endpoint

PFS

Arms

Idelalisib plus rituximab (experimental): Rituximab plus idelalisib 150 mg twice daily
Placebo plus rituximab (control): Rituximab plus placebo twice daily

People

Furman RR

PFSHR 0.15Δ ORR+68 pointsOSHR 0.28Δ 12-month OS+12 points

Show the numbers

Results reported for Idelalisib and rituximab in relapsed chronic lymphocytic leukemia
Endpoint	Analysis	Idelalisib plus rituximab	Placebo plus rituximab	Effect
PFSRandomly assigned patients (n=220); the abstract does not state the analysis population	interimFurman 2014	—	median 5.5 months	HR 0.15P<0.001Median PFS not reached with idelalisib-rituximab. Interim analysis at which the study was stopped early.
ORRRandomly assigned patients (n=220); the abstract does not state the analysis population	interimFurman 2014	81%	13%	P<0.001Odds ratio 29.92.
OSRandomly assigned patients (n=220); the abstract does not state the analysis population	interimFurman 2014	92% at 12 mo	80% at 12 mo	HR 0.28P=0.02Overall survival at 12 months.

Results reported for Idelalisib and rituximab in relapsed chronic lymphocytic leukemia
Endpoint	Analysis	Idelalisib plus rituximab	Placebo plus rituximab	Effect
PFSRandomly assigned patients (n=220); the abstract does not state the analysis population	interimFurman 2014	—	median 5.5 months	HR 0.15P<0.001Median PFS not reached with idelalisib-rituximab. Interim analysis at which the study was stopped early.
ORRRandomly assigned patients (n=220); the abstract does not state the analysis population	interimFurman 2014	81%	13%	P<0.001Odds ratio 29.92.
OSRandomly assigned patients (n=220); the abstract does not state the analysis population	interimFurman 2014	92% at 12 mo	80% at 12 mo	HR 0.28P=0.02Overall survival at 12 months.

Illustrative — modelled from reported values, not trial data. PFS, interim.

Show curves

Placebo plus rituximab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus rituximab
0	100.0%
3	68.5%
7	41.4%
10	28.4%
14	17.1%

Appears in

2021 PI3K inhibitors: CLL approvals, lymphoma indications withdrawn

Sources

Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.
PubMed DOI