A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01203930
• Collaborator: (none)
• Enrollment: 105
• Locations: 6
• Arm: 1
• Actual Duration (Months): 68
• Patients Per Site: 17.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study is to evaluate the safety and clinical activity of idelalisib alone and in combination with rituximab in patients with CLL or SLL.

This Phase 2 study will be the first time that idelalisib is administered to previously untreated patients with hematologic malignancies. Idelalisib has demonstrated clinical activity as a single agent in relapsed or refractory CLL and SLL with acceptable toxicity, which supports its evaluation in previously untreated patients. The study population is limited to patients over 65 years of age because younger patients are generally appropriate for standard immunochemotherapy regimens that are highly active. Since the mechanism of action of idelalisib is distinct from rituximab, it is hypothesized that the combination will be more active than either agent alone. This study will establish initial safety and clinical activity of idelalisib in combination with rituximab in patients with CLL or SLL. Cohort 2 of this study will establish safety and clinical activity of idelalisib alone in subjects with untreated CLL or SLL.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)	Drug: Idelalisib; Drug: Rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Single Arm Study to Investigate the Safety and Clinical Activity of Idelalisib Alone and in Combination With Rituximab in Elderly Subjects With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
• Actual Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Idelalisib This arm consists of 2 cohorts. Participants in Cohort 1 will receive idelalisib for up to twelve 28-day cycles (or development of unacceptable toxicity) plus rituximab (8 doses through the end of Cycle 2). Upon completion of twelve 28-cycles, participants are eligible to remain on idelalisib in a continuation protocol. Participants in Cohort 2 will receive idelalisib until disease progression or development of unacceptable toxicity.

Drug: Idelalisib; Idelalisib 150 mg tablets administered orally twice daily; Other Names: Zydelig® GS-1101 CAL-101 ; Drug: Rituximab; Rituximab 375 mg/m^2 administered intravenously once weekly x 8 weeks; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [Up to 28 Months]

   ORR was assessed based on standardized International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria as specifically modified for this study to reflect current recommendations which consider the mechanism of action of idelalisib and similar drugs, and was defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator. Based on the CLL response definition in the protocol (modified Hallek 2008), the parameters of lymphadenopathy, liver and/or spleen size, constitutional symptoms, polymorphonuclear leukocytes, circulating clonal B-lymphocytes, platelet count, hemoglobin, and marrow were assessed. CR: meeting all defined criteria PR: meeting at least 2 of the criteria of circulating lymphocytes, lymphadenopathy, liver, spleen, or bone marrow (or only lymphadenopathy if liver and spleen normal at baseline) and at least 1 of the criteria for polymorphonuclear leukocytes, platelet count, or hemoglobin.

Secondary Outcome Measures

1. Overall Safety of Idelalisib [Up to 28 Months]

   The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).

2. Lymphadenopathy Response Rate [Baseline and up to 28 Months]

   Lymphadenopathy response rate was defined as the percentage of participants with a ≥ 50% reduction from baseline in the sum of the perpendicular diameters of all measurable lesions while receiving study therapy.

3. Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of All Measurable Lesions [Baseline; Weeks 8, 16, 24, 36, 48, 60, 72, 84, 96, 108, and 120]

4. Duration of Response [Up to 28 Months]

   Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.

5. Progression-Free Survival [Up to 28 Months]

   Progression-free survival (PFS) was defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression or death from any cause. Progression was defined using the Standardized IWCLL criteria as specifically modified for this study to consider the mechanism of action of idelalisib and similar drugs. The occurrence of any of the following events indicated progression: Evidence of any new disease Evidence of worsening of index lesions, spleen or liver, or non-index disease Decrease in platelet count or hemoglobin that is attributable to CLL and is confirmed by bone marrow biopsy

6. Idelalisib Plasma Concentrations (Cohort 1) [Predose and 1.5 hours postdose at Weeks 0, 4, and 24]

7. Idelalisib Plasma Concentrations (Cohort 2) [Predose and 1.5 hours postdose at Weeks 0 and 4 and predose at Weeks 8 and 20]

8. Changes in Potential Pharmacodynamic Markers of Drug Activity in Plasma and Whole Blood [Up to 169 days]

   Changes in potential pharmacodynamic markers of drug activity will include assessments of chemokine and cytokine concentrations, effects on the activity of PI3K and related pathways, and effect on cell migration and other functional outcomes. This endpoint will be assessed at the following time points: Idelalisib+Rituximab (Cohort 1): Predose and 1.5 hour postdose on Day 1 and predose on Days 15, 29, 57, 113, and 169 Idelalisib (Cohort 2): Predose on Days 1, 29, 57, 141

9. Overall Survival [Up to 28 Months]

   Overall survival (OS) is defined as the interval from the start of study treatment to death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Histologically or cytologically confirmed CLL or SLL.

• Age ≥ 65

• Presence of measurable lymphadenopathy (defined as the presence of ≥1 nodal lesion that measures ≥ 1.5 cm in the longest diameter (LD) and ≥ 1.0 cm in the longest perpendicular diameter (LPD) as assessed by physical exam, computed tomography (CT) or magnetic resonance imaging (MRI)).

• CLL - Binet Stage C or Rai Stage III or IV or has active disease defined by meeting at least one of the following criteria:

• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia

• Massive (ie, > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly

• Massive nodes (ie, > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy

• Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time of less than 6 months

• Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy

• At least one of the following disease-related symptoms:

• Unintentional weight loss ≥ 10% within the previous 6 months

• Significant fatigue

• Fevers > 100.4 F for ≥ 2 weeks without other evidence of infection

• Night sweats for ≥ 1 month without evidence of infection

• SLL - has active disease as defined above for CLL, except the lymphocytosis criterion does not apply

• World Health Organization (WHO) Performance Status of ≤ 2

• For men of child-bearing potential, willing to use adequate methods of contraception for the entire duration of the study

• Able to provide written informed consent

Key Exclusion Criteria:

• Prior therapy for CLL or SLL, except corticosteroids for symptom relief

• Treatment with a short course of corticosteroids for symptom relief within 1-week prior to Visit 1

• Known active central nervous system involvement of the malignancy

• Ongoing active, serious infection requiring systemic therapy. Patients may be receiving prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.

• Serum creatinine ≥ 2.0 mg/dL

• Serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) or serum transaminases (ie, aspartate aminotransferase (AST), alanine aminotransferase (ALT)) ≥ 2 x upper limit of normal

• Positive test for human immunodeficiency virus (HIV) antibodies

• Active hepatitis B or C (confirmed by ribonucleic acid (RNA) test). Patients with serologic evidence of prior exposure are eligible.

• History of a non-CLL malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to study entry, 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.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego, Moores Cancer Center	La Jolla	California	United States	92093-0820
2	Stanford University School of Medicine	Stanford	California	United States	94304
3	Columbia University - Herbert Irving Pavilion	New York	New York	United States	10032
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
6	The Universtity of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01203930
• Other Study ID Numbers: 101-08
• First Posted: Sep 17, 2010
• Last Update Posted: Nov 16, 2018
• Last Verified: May 1, 2017

• 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: CLL; SLL; GS-1101; CAL-101; Phosphatidylinositol 3-kinase (PI3K); Rituximab; Rituxan
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Idelalisib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in the United States. The first participant was screened on 28 September 2010. The last study visit occurred on 07 June 2016.
Pre-assignment Detail	113 participants were screened.

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Period Title: Overall Study
STARTED	64	41
COMPLETED	43	0
NOT COMPLETED	21	41

Baseline Characteristics

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)	Total
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses. Participants who completed 12 cycles of idelalisib were eligible to continue treatment on an extension study (101-99).	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity	Total of all reporting groups
Overall Participants	64	41	105
Age, Customized (participants) [Number]
< 70 Years	29 45.3%	14 34.1%	43 41%
≥ 70 Years	35 54.7%	27 65.9%	62 59%
Sex: Female, Male (Count of Participants)
Female	24 37.5%	9 22%	33 31.4%
Male	40 62.5%	32 78%	72 68.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2.4%	1 1%
Not Hispanic or Latino	64 100%	40 97.6%	104 99%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White/Caucasian	61 95.3%	40 97.6%	101 96.2%
Black or African American	1 1.6%	1 2.4%	2 1.9%
Asian	1 1.6%	0 0%	1 1%
Other	1 1.6%	0 0%	1 1%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	ORR was assessed based on standardized International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria as specifically modified for this study to reflect current recommendations which consider the mechanism of action of idelalisib and similar drugs, and was defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator. Based on the CLL response definition in the protocol (modified Hallek 2008), the parameters of lymphadenopathy, liver and/or spleen size, constitutional symptoms, polymorphonuclear leukocytes, circulating clonal B-lymphocytes, platelet count, hemoglobin, and marrow were assessed. CR: meeting all defined criteria PR: meeting at least 2 of the criteria of circulating lymphocytes, lymphadenopathy, liver, spleen, or bone marrow (or only lymphadenopathy if liver and spleen normal at baseline) and at least 1 of the criteria for polymorphonuclear leukocytes, platelet count, or hemoglobin.
Time Frame	Up to 28 Months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Analysis Set: participants who received at least 1 dose of idelalisib.

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	64	41
Number (95% Confidence Interval) [percentage of participants]	96.9 151.4%	87.8 214.1%

2. Secondary Outcome

Title	Overall Safety of Idelalisib
Description	The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).
Time Frame	Up to 28 Months

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	64	41
Any AE	100.0 156.3%	100.0 243.9%
Serious AE	48.4 75.6%	68.3 166.6%
Grade ≥ 3 AE	76.6 119.7%	85.4 208.3%
AE related to idelalisib	81.3 127%	97.6 238%
AE leading to permanent drug discontinuation	28.1 43.9%	56.1 136.8%

3. Secondary Outcome

Title	Lymphadenopathy Response Rate
Description	Lymphadenopathy response rate was defined as the percentage of participants with a ≥ 50% reduction from baseline in the sum of the perpendicular diameters of all measurable lesions while receiving study therapy.
Time Frame	Baseline and up to 28 Months

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with baseline measurable lymph nodes were analyzed.

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	50	38
Number (95% Confidence Interval) [percentage of participants]	98.0 153.1%	86.8 211.7%

4. Secondary Outcome

Title	Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of All Measurable Lesions
Time Frame	Baseline; Weeks 8, 16, 24, 36, 48, 60, 72, 84, 96, 108, and 120

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	50	38
% Change at Wk 8	-100.0	-69.8
% Change at Wk 16	-100.0	-74.5
% Change at Wk 24	-100.0	-76.0
% Change at Wk 36	-100.0	-77.5
% Change at Wk 48	-100.0	-73.9
% Change at Wk 60	-69.7
% Change at Wk 72	-78.0
% Change at Wk 84	-80.0
% Change at Wk 96	-81.3
% Change at Wk 108	-78.1
% Change at Wk 120	-71.9
Best % Change	-100.0	-81.1

5. Secondary Outcome

Title	Duration of Response
Description	Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.
Time Frame	Up to 28 Months

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set who achieved complete or partial response.

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	62	35
Median (95% Confidence Interval) [months]	NA	14.8

6. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-free survival (PFS) was defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression or death from any cause. Progression was defined using the Standardized IWCLL criteria as specifically modified for this study to consider the mechanism of action of idelalisib and similar drugs. The occurrence of any of the following events indicated progression: Evidence of any new disease Evidence of worsening of index lesions, spleen or liver, or non-index disease Decrease in platelet count or hemoglobin that is attributable to CLL and is confirmed by bone marrow biopsy
Time Frame	Up to 28 Months

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	64	41
Median (95% Confidence Interval) [months]	NA	26.2

7. Secondary Outcome

Title	Idelalisib Plasma Concentrations (Cohort 1)
Time Frame	Predose and 1.5 hours postdose at Weeks 0, 4, and 24

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set: participants in the ITT Analysis Set from Cohort 1 who had the necessary baseline and on-study measurements to provide interpretable results for the specific parameters of interest.

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses
Measure Participants	64
Week 0 predose	0.0
Week 0 postdose	1710.0
Week 4 predose	305.0
Week 4 postdose	1720.0
Week 24 predose	256.5
Week 24 postdose	1460.0

8. Secondary Outcome

Title	Idelalisib Plasma Concentrations (Cohort 2)
Time Frame	Predose and 1.5 hours postdose at Weeks 0 and 4 and predose at Weeks 8 and 20

Outcome Measure Data

Analysis Population Description

PK Analysis Set: participants in the ITT Analysis Set from Cohort 2 who had the necessary baseline and on-study measurements to provide interpretable results for the specific parameters of interest.

Arm/Group Title	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	40
Week 0 predose	0.0
Week 0 postdose	2190.0
Week 4 predose	293.0
Week 4 postdose	2120.0
Week 8 predose	453.0
Week 20 predose	590.0

9. Secondary Outcome

Title	Changes in Potential Pharmacodynamic Markers of Drug Activity in Plasma and Whole Blood
Description	Changes in potential pharmacodynamic markers of drug activity will include assessments of chemokine and cytokine concentrations, effects on the activity of PI3K and related pathways, and effect on cell migration and other functional outcomes. This endpoint will be assessed at the following time points: Idelalisib+Rituximab (Cohort 1): Predose and 1.5 hour postdose on Day 1 and predose on Days 15, 29, 57, 113, and 169 Idelalisib (Cohort 2): Predose on Days 1, 29, 57, 141
Time Frame	Up to 169 days

Outcome Measure Data

Analysis Population Description

The collection of plasma samples for pharmacodynamic (PD) analysis in this study was planned prior to the availability of results from an identical PD analysis in another idelalisib study with a larger sample size (n = 176 unique subjects with 2085 longitudinal plasma samples). Therefore, PD analysis was not performed in this study (n = 41).

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses. Participants who completed 12 cycles of idelalisib were eligible to continue treatment on an extension study (101-99).	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	0	0

10. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) is defined as the interval from the start of study treatment to death from any cause.
Time Frame	Up to 28 Months

Outcome Measure Data

Analysis Population Description

Overall survival analysis was not performed because the follow-up period was insufficient to capture enough events.

Arm/Group Title	Idelalisib+Rituximab (Cohort 1)	Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses. Participants who completed 12 cycles of idelalisib were eligible to continue treatment on an extension study (101-99).	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
Measure Participants	0	0

Adverse Events

Time Frame	Up to 28 Months
Adverse Event Reporting Description	Adverse events were coded according to MedDRA Version 15.1 for Cohort 1 and MedDRA Version 19.0 for Cohort 2.
Arm/Group Title	Idelalisib+Rituximab (Cohort 1)		Idelalisib (Cohort 2)
Arm/Group Description	Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle for 12 cycles + rituximab 375 mg/m^2 administered intravenously weekly for 8 doses		Idelalisib 150 mg capsules or tablets administered orally twice daily of each 28-day cycle until disease progression or unacceptable toxicity
All Cause Mortality
	Idelalisib+Rituximab (Cohort 1)		Idelalisib (Cohort 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Idelalisib+Rituximab (Cohort 1)		Idelalisib (Cohort 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/64 (48.4%)		28/41 (68.3%)
Blood and lymphatic system disorders
Anaemia	1/64 (1.6%)		1/41 (2.4%)
Aplasia pure red cell	1/64 (1.6%)		0/41 (0%)
Febrile neutropenia	2/64 (3.1%)		2/41 (4.9%)
Neutropenia	0/64 (0%)		1/41 (2.4%)
Thrombocytopenia	0/64 (0%)		1/41 (2.4%)
Cardiac disorders
Sinus node dysfunction	0/64 (0%)		1/41 (2.4%)
Gastrointestinal disorders
Abdominal distension	0/64 (0%)		1/41 (2.4%)
Colitis	6/64 (9.4%)		4/41 (9.8%)
Diarrhoea	6/64 (9.4%)		7/41 (17.1%)
Intestinal obstruction	1/64 (1.6%)		0/41 (0%)
Small intestinal obstruction	1/64 (1.6%)		0/41 (0%)
General disorders
Asthenia	1/64 (1.6%)		0/41 (0%)
Chest pain	1/64 (1.6%)		0/41 (0%)
Face oedema	0/64 (0%)		1/41 (2.4%)
Fatigue	0/64 (0%)		1/41 (2.4%)
Impaired healing	1/64 (1.6%)		0/41 (0%)
Pyrexia	2/64 (3.1%)		3/41 (7.3%)
Infections and infestations
Cellulitis	1/64 (1.6%)		2/41 (4.9%)
Clostridial infection	1/64 (1.6%)		0/41 (0%)
Cytomegalovirus oesophagitis	0/64 (0%)		1/41 (2.4%)
Oesophageal candidiasis	1/64 (1.6%)		1/41 (2.4%)
Oral candidiasis	1/64 (1.6%)		0/41 (0%)
Pneumocystis jiroveci pneumonia	1/64 (1.6%)		0/41 (0%)
Pneumocystis jirovecii pneumonia	0/64 (0%)		1/41 (2.4%)
Pneumonia	8/64 (12.5%)		5/41 (12.2%)
Sepsis	0/64 (0%)		1/41 (2.4%)
Urinary tract infection	1/64 (1.6%)		0/41 (0%)
Urosepsis	1/64 (1.6%)		0/41 (0%)
Injury, poisoning and procedural complications
Arterial injury	1/64 (1.6%)		0/41 (0%)
Infusion related reaction	1/64 (1.6%)		0/41 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/64 (0%)		1/41 (2.4%)
Dehydration	1/64 (1.6%)		2/41 (4.9%)
Hypercalcaemia	1/64 (1.6%)		0/41 (0%)
Hypoglycaemia	0/64 (0%)		1/41 (2.4%)
Hypokalaemia	0/64 (0%)		1/41 (2.4%)
Musculoskeletal and connective tissue disorders
Back pain	0/64 (0%)		1/41 (2.4%)
Muscular weakness	0/64 (0%)		1/41 (2.4%)
Musculoskeletal pain	1/64 (1.6%)		0/41 (0%)
Rhabdomyolysis	0/64 (0%)		1/41 (2.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma	1/64 (1.6%)		0/41 (0%)
Nervous system disorders
Balance disorder	1/64 (1.6%)		0/41 (0%)
Syncope	0/64 (0%)		1/41 (2.4%)
Psychiatric disorders
Confusional state	1/64 (1.6%)		0/41 (0%)
Renal and urinary disorders
Acute kidney injury	0/64 (0%)		1/41 (2.4%)
Renal failure acute	1/64 (1.6%)		0/41 (0%)
Urinary retention	0/64 (0%)		1/41 (2.4%)
Reproductive system and breast disorders
Testicular pain	1/64 (1.6%)		0/41 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/64 (0%)		1/41 (2.4%)
Cough	0/64 (0%)		2/41 (4.9%)
Dyspnoea	2/64 (3.1%)		1/41 (2.4%)
Hypoxia	2/64 (3.1%)		0/41 (0%)
Organising pneumonia	1/64 (1.6%)		0/41 (0%)
Pneumonitis	2/64 (3.1%)		2/41 (4.9%)
Pulmonary fibrosis	2/64 (3.1%)		0/41 (0%)
Respiratory failure	2/64 (3.1%)		0/41 (0%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	0/64 (0%)		1/41 (2.4%)
Vascular disorders
Embolism	0/64 (0%)		1/41 (2.4%)
Hypertension	1/64 (1.6%)		0/41 (0%)
Hypotension	0/64 (0%)		1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Idelalisib+Rituximab (Cohort 1)		Idelalisib (Cohort 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/64 (98.4%)		40/41 (97.6%)
Blood and lymphatic system disorders
Anaemia	5/64 (7.8%)		8/41 (19.5%)
Neutropenia	3/64 (4.7%)		9/41 (22%)
Thrombocytopenia	0/64 (0%)		10/41 (24.4%)
Gastrointestinal disorders
Abdominal pain	7/64 (10.9%)		1/41 (2.4%)
Abdominal pain upper	5/64 (7.8%)		0/41 (0%)
Colitis	2/64 (3.1%)		3/41 (7.3%)
Constipation	11/64 (17.2%)		12/41 (29.3%)
Diarrhoea	31/64 (48.4%)		27/41 (65.9%)
Dry mouth	1/64 (1.6%)		4/41 (9.8%)
Flatulence	4/64 (6.3%)		3/41 (7.3%)
Mouth ulceration	0/64 (0%)		4/41 (9.8%)
Nausea	24/64 (37.5%)		14/41 (34.1%)
Stomatitis	7/64 (10.9%)		1/41 (2.4%)
Vomiting	14/64 (21.9%)		7/41 (17.1%)
General disorders
Asthenia	7/64 (10.9%)		0/41 (0%)
Chest discomfort	4/64 (6.3%)		0/41 (0%)
Chills	23/64 (35.9%)		6/41 (14.6%)
Fatigue	20/64 (31.3%)		13/41 (31.7%)
Influenza like illness	8/64 (12.5%)		1/41 (2.4%)
Malaise	6/64 (9.4%)		1/41 (2.4%)
Oedema	4/64 (6.3%)		2/41 (4.9%)
Oedema peripheral	8/64 (12.5%)		10/41 (24.4%)
Peripheral swelling	0/64 (0%)		3/41 (7.3%)
Pyrexia	26/64 (40.6%)		13/41 (31.7%)
Infections and infestations
Candida infection	0/64 (0%)		3/41 (7.3%)
Pneumonia	7/64 (10.9%)		4/41 (9.8%)
Sinusitis	6/64 (9.4%)		2/41 (4.9%)
Upper respiratory tract infection	7/64 (10.9%)		11/41 (26.8%)
Urinary tract infection	9/64 (14.1%)		2/41 (4.9%)
Injury, poisoning and procedural complications
Infusion related reaction	6/64 (9.4%)		0/41 (0%)
Investigations
Alanine aminotransferase increased	18/64 (28.1%)		11/41 (26.8%)
Aspartate aminotransferase increased	17/64 (26.6%)		10/41 (24.4%)
Blood alkaline phosphatase increased	2/64 (3.1%)		3/41 (7.3%)
Liver function test abnormal	6/64 (9.4%)		0/41 (0%)
Neutrophil count decreased	2/64 (3.1%)		3/41 (7.3%)
Transaminases increased	9/64 (14.1%)		0/41 (0%)
Weight decreased	6/64 (9.4%)		2/41 (4.9%)
Metabolism and nutrition disorders
Decreased appetite	9/64 (14.1%)		2/41 (4.9%)
Dehydration	6/64 (9.4%)		2/41 (4.9%)
Hypercalcaemia	1/64 (1.6%)		3/41 (7.3%)
Hypocalcaemia	1/64 (1.6%)		4/41 (9.8%)
Hypokalaemia	6/64 (9.4%)		6/41 (14.6%)
Hypomagnesaemia	4/64 (6.3%)		8/41 (19.5%)
Hypophosphataemia	1/64 (1.6%)		5/41 (12.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/64 (15.6%)		7/41 (17.1%)
Back pain	9/64 (14.1%)		3/41 (7.3%)
Muscle spasms	4/64 (6.3%)		5/41 (12.2%)
Musculoskeletal pain	4/64 (6.3%)		2/41 (4.9%)
Myalgia	4/64 (6.3%)		3/41 (7.3%)
Pain in extremity	6/64 (9.4%)		4/41 (9.8%)
Nervous system disorders
Dizziness	7/64 (10.9%)		1/41 (2.4%)
Dysgeusia	4/64 (6.3%)		0/41 (0%)
Headache	15/64 (23.4%)		5/41 (12.2%)
Psychiatric disorders
Anxiety	4/64 (6.3%)		6/41 (14.6%)
Insomnia	13/64 (20.3%)		2/41 (4.9%)
Renal and urinary disorders
Renal failure acute	4/64 (6.3%)		0/41 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	21/64 (32.8%)		11/41 (26.8%)
Dyspnoea	13/64 (20.3%)		4/41 (9.8%)
Rhinorrhoea	1/64 (1.6%)		4/41 (9.8%)
Skin and subcutaneous tissue disorders
Dry skin	1/64 (1.6%)		6/41 (14.6%)
Erythema	0/64 (0%)		3/41 (7.3%)
Night sweats	10/64 (15.6%)		5/41 (12.2%)
Pruritus	10/64 (15.6%)		5/41 (12.2%)
Rash	24/64 (37.5%)		14/41 (34.1%)
Rash maculo-papular	1/64 (1.6%)		7/41 (17.1%)
Vascular disorders
Flushing	4/64 (6.3%)		1/41 (2.4%)
Hypertension	3/64 (4.7%)		3/41 (7.3%)
Hypotension	7/64 (10.9%)		4/41 (9.8%)

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