DELTA: Efficacy and Safety Study of Idelalisib in Participants With Indolent B-Cell Non-Hodgkin Lymphomas

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01282424
• Collaborator: (none)
• Enrollment: 125
• Locations: 41
• Arm: 1
• Actual Duration (Months): 85.9
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective will be to assess the overall response rate and to evaluate the efficacy and safety of idelalisib (IDELA; GS-1101) in participants with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy.

Eligible participants will initiate oral therapy with idelalisib at a starting dose of 150 mg taken twice per day. Treatment with idelalisib can continue in compliant participants as long as the study is still ongoing and the participants appear to be benefiting from treatment with acceptable safety.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma; Small Lymphocytic Lymphoma; Lymphoplasmacytic Lymphoma; Marginal Zone Lymphoma	Drug: Idelalisib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study to Assess the Efficacy and Safety of Idelalisib in Subjects With Indolent B-Cell Non-Hodgkin Lymphomas Refractory to Rituximab and Alkylating Agents
• Actual Study Start Date: Mar 18, 2011
• Actual Primary Completion Date: May 2, 2018
• Actual Study Completion Date: May 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Idelalisib Treatment with idelalisib will be continued until tumor progression or development of unacceptable toxicity.	Drug: Idelalisib; Idelalisib 150 mg tablet administered orally twice daily; Other Names: Zydelig® GS-1101 CAL-101 IDELA

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [Start of Treatment to End of Treatment (up to 81 months)]

   Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) or partial response (PR; or minor response [MR] for participants with WM) as assessed by the study independent review committee (IRC). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. For WM only, response was defined as a reduction in immunoglobulin M (IgM) of ≥ 50% decrease for PR, and ≥ 25% decrease for MR; no increase from baseline in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions or signs and symptoms of active disease (Owen, 2013)

Secondary Outcome Measures

1. Duration of Response [Start of Treatment to End of Treatment (up to 81 months)]

   Duration of Response (DOR) was defined as the interval from the first documentation of CR or PR (or MR for participants with WM) to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.

2. Lymph Node Response Rate [Start of Treatment to End of Treatment (up to 81 months)]

   Lymph node response (LNR) was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions as assessed by the study IRC.

3. Time to Response [Start of Treatment to End of Treatment (up to 81 months)]

   Time to response (TTR) was defined as the interval from the start of idelalisib treatment to the first documentation of CR or PR (or MR for participants with WM) as assessed by the study IRC.

4. Progression-Free Survival [Start of Treatment to End of Treatment (up to 81 months)]

   Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. PFS was analyzed using KM estimates.

5. Overall Survival [Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)]

   Overall survival (OS) was defined as the time interval from the start of idelalisib treatment to death from any cause. OS was analyzed using KM estimates.

6. Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) [Baseline to End of Treatment (up to 81 months)]

   Change in health-related quality of life events were reported by participants using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) assessment tool. Results are presented as the mean (SD) best change from baseline. The best change from baseline was defined as the highest change score (improvement) after baseline. The FACT-LymS is on a scale from 0-60, with higher scores associated with a better quality of life. It incorporates values from 15 questions, each rated 0-4, related to study indications.

7. Change in Karnofsky Performance Status [Baseline to End of Treatment (up to 81 months)]

   The change in Karnofsky performance status was reported as the best (highest change score) and worst (lowest change score) change from baseline using the Karnofsky performance criteria. The Karnofsky score classified participants according to their functional impairment. Scores are on a scale from 0-100, the lower the score, the worse the survival for most serious illnesses.

8. Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines [Enrollment to End of Treatment (up to 81 months)]

   Analysis of the cytokine/chemokine was planned to be performed on a subset of samples from this study along with a subset of samples from other studies. Therefore, data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

9. Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms [Start of Treatment to End of Treatment (up to 81 months) plus 30 days]

   This composite endpoint measured the safety and tolerability profile of idelalisib. "Clinically meaningful" abnormalities in vital signs and electrocardiograms (ECG) were as determined by the investigator.

10. Study Drug Exposure [Start of Treatment to End of Treatment (up to 81 months)]

    The average idelalisib exposure was summarized.

11. Idelalisib Plasma Concentration [Predose and at 1.5 hours (± 5 minutes) postdose on Day 29]

12. PK Parameter: Cmax [Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29]

    Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.

13. PK Parameter: Tmax [Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29]

    Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).

14. PK Parameter: AUClast [Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29]

    AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Karnofsky performance status of ≥ 60 (Eastern Cooperative Oncology Group [ECOG] performance score of 0, 1, or 2)

• Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:

• Follicular lymphoma (FL)

• Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10^9/L at the time of diagnosis and on baseline laboratory assessment performed within 4 weeks prior to the start of study drug administration

• Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)

• Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)

• Prior treatment with ≥ 2 prior chemotherapy-based or immunotherapy-based regimens for iNHL

• Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy

• Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL

• Lymphoma that is refractory to rituximab and to an alkylating agent

• Discontinuation of all other therapies for treatment of iNHL ≥ 3 weeks before Visit 2

• For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods

• Willingness and ability to provide written informed consent and to comply with the protocol requirements

Key Exclusion Criteria:

• Central nervous system or leptomeningeal lymphoma

• Known histological transformation from iNHL to diffuse large B-cell lymphoma

• History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years

• Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment

• Pregnancy or breastfeeding

• Ongoing alcohol or drug addiction

• Known history of drug-induced liver injury, chronic active hepatitis B infection, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension

• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation

• Ongoing immunosuppressive therapy, including systemic corticosteroids. Participant may be using topical or inhaled corticosteroids.

• Prior therapy with idelalisib

• Exposure to another investigational drug within 3 weeks prior to start of study treatment

• Concurrent participation in another therapeutic treatment trial

• Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, alter the absorption, distribution, metabolism or excretion of the study drug, or impair the assessment of study results

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Medical Center	Fullerton	California	United States	92835
2	Pacific Shores Medical Group	Long Beach	California	United States	90813-3244
3	UCLA	Los Angeles	California	United States	90095
4	Central Coast Medical Oncology	Santa Maria	California	United States	93454
5	Stanford Cancer Center	Stanford	California	United States	94035-5796
6	Collaborative Research Group, LLC	Boynton Beach	Florida	United States	33435
7	Winship Cancer Institute	Atlanta	Georgia	United States	30322-1013
8	Northwestern University Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois	United States	60611
9	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
10	John Theurer Cancer Center Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
11	University of Medicine and Dentistry of NJ	New Brunswick	New Jersey	United States	08901-1914
12	Weill Cornell -New York Presbyterian Hospital	New York	New York	United States	10002
13	Montefiore Medical Center	New York	New York	United States	10467
14	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
15	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
16	South Carolina Oncology Associates	Columbia	South Carolina	United States	29210
17	Chattanooga Hem/Oncology Ass (SCRI)	Chattanooga	Tennessee	United States	37404
18	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
19	Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
20	University of Virginia Medical Center	Charlottesville	Virginia	United States	22908
21	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
22	University of Wisconsin	Madison	Wisconsin	United States	53792-5156
23	CHU Morvan	Brest		France	29609
24	Centre Hospitalier de Lyon Sud	Pierre Benite		France	69310
25	Centre Henri Bequerel	Rouen		France	76038
26	CHU Bretonneau - Centre Kaplan	Tours		France	37044
27	Charité Campus Virchow Klinikum	Berlin		Germany	13353
28	Universitätsklinikum Essen	Essen		Germany	45147
29	Klinikum der Universität München-Großhadern	München		Germany	81377
30	Universitatsklinikum Ulm	Ulm		Germany	89081
31	Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi	Bologna		Italy	40138
32	A.O.U. San Martino	Genova		Italy	16132
33	Fondazione Centro San Raffaele del Monte Tabor	Milano		Italy	20132
34	Università "Sapienza"	Rome		Italy	00161
35	Małopolskie Centrum Medyczne	Kraków		Poland	30-510
36	Centrum Onkologii w Warszawie	Warsaw		Poland	02-781
37	St James's Institute of Oncology	Leeds		United Kingdom	LS9 7TF
38	St Bartholemews Hospital	London		United Kingdom	EC1M 6BQ
39	Sarah Cannon Institute	London		United Kingdom	W1G 6AD
40	The Christie Hospital	Manchester		United Kingdom	M20 4BX
41	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Statistical Analysis Plan - Jul 8, 2013
• Study Protocol: Amendment 10 (Version 9.0) - Sep 5, 2017

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01282424
• Other Study ID Numbers: 101-09; 2010-022155-33
• First Posted: Jan 25, 2011
• Last Update Posted: Jul 11, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gilead Sciences: indolent Non-Hodgkin Lymphoma; Non-Hodgkin Lymphoma; iNHL; NHL; GS-1101; CAL-101; PI3K; Phosphatidylinositol 3-kinase; Follicular Lymphoma (FL); Small lymphocytic lymphoma (SLL); Lymphoplasmacytoid lymphoma (LPL); Marginal zone lymphoma (MZL)
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Waldenstrom Macroglobulinemia; Idelalisib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 54 study sites in North America and Europe. The first participant was screened on 04 March 2011. The last participant observation was on 16 May 2018.
Pre-assignment Detail	125 participants were enrolled and treated and comprise the Intent-to-Treat (ITT) Analysis Set.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Period Title: Treatment Period (TP) (81 Months)
STARTED	125
Completed: Disease Progression	70
Completed: Death	9
COMPLETED	79
NOT COMPLETED	46
Period Title: Treatment Period (TP) (81 Months)
STARTED	84
COMPLETED	20
NOT COMPLETED	64

Baseline Characteristics

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Overall Participants	125
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (11.4)
Sex: Female, Male (Count of Participants)
Female	45 36%
Male	80 64%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	110 88%
Black or African American	2 1.6%
Asian	3 2.4%
American Indian or Alaska Native	1 0.8%
Other	8 6.4%
Missing	1 0.8%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	6 4.8%
Not Hispanic or Latino	117 93.6%
Missing	2 1.6%
Region of Enrollment (Count of Participants)
France	10 8%
United States	83 66.4%
Poland	8 6.4%
Germany	10 8%
United Kingdom	8 6.4%
Italy	6 4.8%
Karnofsky Performance Status (Count of Participants)
Score = 60	2 1.6%
Score = 70	6 4.8%
Score = 80	27 21.6%
Score = 90	44 35.2%
Score = 100	46 36.8%
Baseline Disease History (Count of Participants)
Folicular lymphoma	72 57.6%
Small lymphocytic lymphoma	28 22.4%
LPL/WM	10 8%
Marginal zone lymphoma	15 12%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) or partial response (PR; or minor response [MR] for participants with WM) as assessed by the study independent review committee (IRC). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. For WM only, response was defined as a reduction in immunoglobulin M (IgM) of ≥ 50% decrease for PR, and ≥ 25% decrease for MR; no increase from baseline in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions or signs and symptoms of active disease (Owen, 2013)
Time Frame	Start of Treatment to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

ITT Analysis Set included enrolled participants who received at least one dose of study drug.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	125
Number (95% Confidence Interval) [percentage of participants]	57.6 46.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Idelalisib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The null hypothesis is ≤ 20%.
	Method	Exact binomial test
	Comments

2. Secondary Outcome

Title	Duration of Response
Description	Duration of Response (DOR) was defined as the interval from the first documentation of CR or PR (or MR for participants with WM) to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.
Time Frame	Start of Treatment to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set who achieved a CR or PR (or MR for participants with WM) were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	72
Median (Inter-Quartile Range) [months]	12.5

3. Secondary Outcome

Title	Lymph Node Response Rate
Description	Lymph node response (LNR) was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions as assessed by the study IRC.
Time Frame	Start of Treatment to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	125
Number (95% Confidence Interval) [percentage of participants]	56.8 45.4%

4. Secondary Outcome

Title	Time to Response
Description	Time to response (TTR) was defined as the interval from the start of idelalisib treatment to the first documentation of CR or PR (or MR for participants with WM) as assessed by the study IRC.
Time Frame	Start of Treatment to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set who achieved a CR or PR (or MR for participants with WM) were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	72
Median (Inter-Quartile Range) [months]	2.0

5. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. PFS was analyzed using KM estimates.
Time Frame	Start of Treatment to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	125
Median (95% Confidence Interval) [months]	11.1

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the time interval from the start of idelalisib treatment to death from any cause. OS was analyzed using KM estimates.
Time Frame	Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	125
Median (95% Confidence Interval) [months]	48.6

7. Secondary Outcome

Title	Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS)
Description	Change in health-related quality of life events were reported by participants using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) assessment tool. Results are presented as the mean (SD) best change from baseline. The best change from baseline was defined as the highest change score (improvement) after baseline. The FACT-LymS is on a scale from 0-60, with higher scores associated with a better quality of life. It incorporates values from 15 questions, each rated 0-4, related to study indications.
Time Frame	Baseline to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	113
Mean (Standard Deviation) [units on a scale]	10.3 (17.08)

8. Secondary Outcome

Title	Change in Karnofsky Performance Status
Description	The change in Karnofsky performance status was reported as the best (highest change score) and worst (lowest change score) change from baseline using the Karnofsky performance criteria. The Karnofsky score classified participants according to their functional impairment. Scores are on a scale from 0-100, the lower the score, the worse the survival for most serious illnesses.
Time Frame	Baseline to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	122
Best change	3.0 (8.71)
Worst change	-10.7 (12.61)

9. Secondary Outcome

Title	Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines
Description	Analysis of the cytokine/chemokine was planned to be performed on a subset of samples from this study along with a subset of samples from other studies. Therefore, data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame	Enrollment to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms
Description	This composite endpoint measured the safety and tolerability profile of idelalisib. "Clinically meaningful" abnormalities in vital signs and electrocardiograms (ECG) were as determined by the investigator.
Time Frame	Start of Treatment to End of Treatment (up to 81 months) plus 30 days

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	125
Any AE	123 98.4%
AE leading to drug discontinuation	35 28%
Serious AE	72 57.6%
Vital signs abnormal - clinically meaningful	0 0%
ECG abnormal - clinically meaningful	0 0%
Grade 3 or 4 hemoglobin	2 1.6%
Grade 3 or 4 neutrophils	35 28%
Grade 3 or 4 platelets	9 7.2%
Grade 3 or 4 alanine aminotransferase	16 12.8%
Grade 3 or 4 aspartate aminotransferase	11 8.8%

11. Secondary Outcome

Title	Study Drug Exposure
Description	The average idelalisib exposure was summarized.
Time Frame	Start of Treatment to End of Treatment (up to 81 months)

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	125
Mean (Standard Deviation) [months]	13.2 (15.08)

12. Secondary Outcome

Title	Idelalisib Plasma Concentration
Time Frame	Predose and at 1.5 hours (± 5 minutes) postdose on Day 29

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included participants in the ITT Analysis Set who had the necessary baseline and on-study measurements.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	125
Predose	471.6 (486.53)
Postdose	2187.7 (1050.76)

13. Secondary Outcome

Title	PK Parameter: Cmax
Description	Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.
Time Frame	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	8
Cmax at Day 1	2647.5 (1084.99)
Cmax at Day 29	2258.8 (809.61)

14. Secondary Outcome

Title	PK Parameter: Tmax
Description	Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).
Time Frame	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	8
Tmax at Day 1	1.00
Tmax at Day 29	1.00

15. Secondary Outcome

Title	PK Parameter: AUClast
Description	AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration
Time Frame	Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed.

Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
Measure Participants	8
AUClast at Day 1	9094.76 (2960.391)
AUClast at Day 29	9293.39 (3996.826)

Adverse Events

Time Frame	Adverse Events: Start of Treatment to End of Treatment (up to 81 months) plus 30 days; All-Cause Mortality: Baseline to Last Long-Term Follow-Up Visit (up to maximum of 7 years)
Adverse Event Reporting Description	ITT Analysis Set included enrolled participants who received at least one dose of study drug.
Arm/Group Title	Idelalisib
Arm/Group Description	Idelalisib 150 mg tablet administered orally twice daily until tumor progression or development of unacceptable toxicity.
All Cause Mortality
	Idelalisib
	Affected / at Risk (%)	# Events
Total	64/125 (51.2%)
Serious Adverse Events
	Idelalisib
	Affected / at Risk (%)	# Events
Total	72/125 (57.6%)
Blood and lymphatic system disorders
Anaemia	2/125 (1.6%)
Autoimmune haemolytic anaemia	1/125 (0.8%)
Febrile neutropenia	5/125 (4%)
Neutropenia	3/125 (2.4%)
Splenic infarction	1/125 (0.8%)
Thrombocytopenia	1/125 (0.8%)
Cardiac disorders
Acute myocardial infarction	1/125 (0.8%)
Atrial fibrillation	1/125 (0.8%)
Cardiac arrest	1/125 (0.8%)
Cardiac failure	2/125 (1.6%)
Cardiomyopathy	1/125 (0.8%)
Sinus tachycardia	1/125 (0.8%)
Supraventricular tachycardia	1/125 (0.8%)
Eye disorders
Visual impairment	1/125 (0.8%)
Gastrointestinal disorders
Abdominal pain	1/125 (0.8%)
Acute abdomen	1/125 (0.8%)
Autoimmune colitis	1/125 (0.8%)
Colitis	5/125 (4%)
Diarrhoea	11/125 (8.8%)
Enteritis	1/125 (0.8%)
Enterocolitis	1/125 (0.8%)
Gastrointestinal haemorrhage	1/125 (0.8%)
Haemorrhoids	1/125 (0.8%)
Melaena	2/125 (1.6%)
Mouth haemorrhage	1/125 (0.8%)
Nausea	1/125 (0.8%)
Oesophagitis	1/125 (0.8%)
Pancreatitis	1/125 (0.8%)
Rectal haemorrhage	1/125 (0.8%)
Stomatitis	1/125 (0.8%)
Upper gastrointestinal haemorrhage	1/125 (0.8%)
Vomiting	2/125 (1.6%)
General disorders
Asthenia	2/125 (1.6%)
Chest pain	2/125 (1.6%)
Death	1/125 (0.8%)
Multiple organ dysfunction syndrome	2/125 (1.6%)
Peripheral swelling	3/125 (2.4%)
Pyrexia	15/125 (12%)
Hepatobiliary disorders
Cholelithiasis	1/125 (0.8%)
Hepatic function abnormal	1/125 (0.8%)
Immune system disorders
Anaphylactic reaction	1/125 (0.8%)
Autoimmune disorder	1/125 (0.8%)
Infections and infestations
Cellulitis	1/125 (0.8%)
Cytomegalovirus colitis	2/125 (1.6%)
Device related infection	2/125 (1.6%)
Gastroenteritis	1/125 (0.8%)
Herpes zoster	1/125 (0.8%)
Infective exacerbation of chronic obstructive airways disease	1/125 (0.8%)
Lung infection	1/125 (0.8%)
Perirectal abscess	2/125 (1.6%)
Pharyngitis	1/125 (0.8%)
Pneumocystis jirovecii pneumonia	2/125 (1.6%)
Pneumonia	15/125 (12%)
Pneumonia cytomegaloviral	1/125 (0.8%)
Pneumonia necrotising	1/125 (0.8%)
Pneumonia pneumococcal	1/125 (0.8%)
Pneumonia pseudomonal	1/125 (0.8%)
Pneumonia staphylococcal	1/125 (0.8%)
Pneumonia streptococcal	1/125 (0.8%)
Sepsis	2/125 (1.6%)
Sepsis syndrome	1/125 (0.8%)
Septic shock	2/125 (1.6%)
Sinusitis	1/125 (0.8%)
Soft tissue infection	1/125 (0.8%)
Staphylococcal infection	1/125 (0.8%)
Toxoplasmosis	1/125 (0.8%)
Urinary tract infection	2/125 (1.6%)
Varicella zoster virus infection	1/125 (0.8%)
Wound infection	1/125 (0.8%)
Injury, poisoning and procedural complications
Fall	1/125 (0.8%)
Fracture	1/125 (0.8%)
Head injury	1/125 (0.8%)
Hip fracture	1/125 (0.8%)
Limb injury	1/125 (0.8%)
Metabolism and nutrition disorders
Decreased appetite	1/125 (0.8%)
Dehydration	4/125 (3.2%)
Failure to thrive	1/125 (0.8%)
Hypercalcaemia	2/125 (1.6%)
Hypokalaemia	2/125 (1.6%)
Hyponatraemia	1/125 (0.8%)
Metabolic acidosis	1/125 (0.8%)
Musculoskeletal and connective tissue disorders
Back pain	1/125 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/125 (0.8%)
Basal cell carcinoma	1/125 (0.8%)
Gastric cancer	1/125 (0.8%)
Skin cancer	1/125 (0.8%)
Squamous cell carcinoma	2/125 (1.6%)
Nervous system disorders
Cerebral ischaemia	1/125 (0.8%)
Cerebrovascular accident	1/125 (0.8%)
Paraplegia	1/125 (0.8%)
Psychiatric disorders
Anxiety	1/125 (0.8%)
Renal and urinary disorders
Acute kidney injury	4/125 (3.2%)
Hydronephrosis	1/125 (0.8%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	2/125 (1.6%)
Dyspnoea	3/125 (2.4%)
Interstitial lung disease	1/125 (0.8%)
Lung infiltration	1/125 (0.8%)
Pleural effusion	2/125 (1.6%)
Pneumonia aspiration	2/125 (1.6%)
Pneumonitis	3/125 (2.4%)
Pulmonary embolism	1/125 (0.8%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised	1/125 (0.8%)
Erythema	1/125 (0.8%)
Rash	1/125 (0.8%)
Vascular disorders
Deep vein thrombosis	1/125 (0.8%)
Hypotension	2/125 (1.6%)
Lymphorrhoea	1/125 (0.8%)
Other (Not Including Serious) Adverse Events
	Idelalisib
	Affected / at Risk (%)	# Events
Total	123/125 (98.4%)
Blood and lymphatic system disorders
Anaemia	18/125 (14.4%)
Leukopenia	9/125 (7.2%)
Neutropenia	35/125 (28%)
Thrombocytopenia	23/125 (18.4%)
Gastrointestinal disorders
Abdominal pain	21/125 (16.8%)
Abdominal pain upper	10/125 (8%)
Constipation	11/125 (8.8%)
Diarrhoea	59/125 (47.2%)
Dysphagia	7/125 (5.6%)
Nausea	38/125 (30.4%)
Stomatitis	8/125 (6.4%)
Vomiting	20/125 (16%)
General disorders
Asthenia	14/125 (11.2%)
Chills	11/125 (8.8%)
Fatigue	40/125 (32%)
Mucosal inflammation	8/125 (6.4%)
Oedema peripheral	13/125 (10.4%)
Pain	9/125 (7.2%)
Pyrexia	34/125 (27.2%)
Infections and infestations
Bronchitis	7/125 (5.6%)
Herpes zoster	7/125 (5.6%)
Pneumonia	8/125 (6.4%)
Upper respiratory tract infection	23/125 (18.4%)
Urinary tract infection	8/125 (6.4%)
Investigations
Alanine aminotransferase increased	18/125 (14.4%)
Aspartate aminotransferase increased	16/125 (12.8%)
Blood creatinine increased	9/125 (7.2%)
Blood lactate dehydrogenase increased	7/125 (5.6%)
Weight decreased	19/125 (15.2%)
Metabolism and nutrition disorders
Decreased appetite	23/125 (18.4%)
Dehydration	10/125 (8%)
Hyperglycaemia	11/125 (8.8%)
Hypocalcaemia	7/125 (5.6%)
Hypokalaemia	15/125 (12%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/125 (6.4%)
Back pain	13/125 (10.4%)
Nervous system disorders
Dizziness	11/125 (8.8%)
Dysgeusia	7/125 (5.6%)
Headache	17/125 (13.6%)
Psychiatric disorders
Insomnia	12/125 (9.6%)
Respiratory, thoracic and mediastinal disorders
Cough	40/125 (32%)
Dyspnoea	22/125 (17.6%)
Oropharyngeal pain	11/125 (8.8%)
Pleural effusion	7/125 (5.6%)
Skin and subcutaneous tissue disorders
Dry skin	9/125 (7.2%)
Night sweats	18/125 (14.4%)
Pruritus	9/125 (7.2%)
Rash	18/125 (14.4%)
Vascular disorders
Hypertension	9/125 (7.2%)
Hypotension	8/125 (6.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years