Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Adults With Metastatic Pancreatic Ductal Adenocarcinoma

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02468557
• Collaborator: (none)
• Enrollment: 16
• Locations: 9
• Arms: 3
• Actual Duration (Months): 8.9
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety of single agent idelalisib and to evaluate safety and define the maximum tolerated dose (MTD) of idelalisib in combination with chemotherapy in adults with metastatic pancreatic ductal adenocarcinoma.

Condition or Disease	Intervention/Treatment	Phase
Previously Untreated Pancreatic Ductal Adenocarcinoma; Relapsed/Refractory Pancreatic Ductal Adenocarcinoma	Drug: Idelalisib; Drug: Nab-paclitaxel; Drug: mFOLFOX6	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma
• Actual Study Start Date: Jul 30, 2015
• Actual Primary Completion Date: Apr 27, 2016
• Actual Study Completion Date: Apr 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Idelalisib 150 mg Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.	Drug: Idelalisib; Tablets administered orally twice daily; Other Names: GS-1101 CAL-101 Zydelig®
Experimental: Idelalisib + nab-paclitaxel Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + nab-paclitaxel.	Drug: Idelalisib; Tablets administered orally twice daily; Other Names: GS-1101 CAL-101 Zydelig® ; Drug: Nab-paclitaxel; 125 mg/m^2 administered intravenously on Days 1, 8 and 15 of each 28 day cycle
Experimental: Idelalisib + mFOLFOX6 Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + mFOLFOX6.	Drug: Idelalisib; Tablets administered orally twice daily; Other Names: GS-1101 CAL-101 Zydelig® ; Drug: mFOLFOX6; mFOLFOX6 will be administered intravenously on Days 1 and 15 of each 28 day cycle. This regimen consists of levoleucovorin 200 milligram/meter per square (mg/m^2) or racemic leucovorin 400 mg/m^2, oxaliplatin 85 mg/m^2, bolus 5-fluorouracil 400 mg/m^2, and a 46 hour infusion of 5-fluorouracil 2, 400 mg/m^2.

Outcome Measures

Primary Outcome Measures

1. Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) [First dose date up to last dose date (Maximum: 8 weeks) plus 30 days]

   TEAEs were defined as adverse events (AEs) with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the study drug. It also included the AEs that led to premature discontinuation of study drug.

2. Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities [First dose date up to last dose date (Maximum: 8 weeks) plus 30 days]

   Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post baseline time point, up to and including the date of last dose of study drug plus 30 days. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Severity grade is defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening). The percentage of participants for any post-baseline abnormal laboratory value in the Grade 1-4 category is reported. The term 'hypo' indicates less than the normal count of a parameter and 'hyper' indicates more than the normal count of a parameter.

3. Idelalisib in Combination With Chemotherapy: Percentage of Participants With Dose Limiting Toxicities (DLTs) [Up to 28 days]

   Dose limiting toxicities were defined as toxicities experienced during the first 28 days of treatment (Cycle 1) that were judged to be clinically significant and at least possibly related to study treatment.

Secondary Outcome Measures

1. Change From Baseline in FoxP3+ and Cluster Determinant 8+ (CD8+) Cells From Tumor Tissue Samples as a Measure of Pharmacodynamics Activity [Up to 2 years]

2. Idelalisib Plasma Concentrations Following Idelalisib 150 mg Twice Daily [Cycle 1, Day 1: Predose and 0.5, 1, 1.5, 2, 3, 4, and 8 hours (h) postdose; Day 8: Predose and 1.5 h postdose; Day 15: Predose and 1.5 h postdose Cycle 2, Day 1: Predose and 1.5 h postdose]

3. Idelalisib Metabolite (GS-563117) Plasma Concentrations Following Idelalisib 150 mg Twice Daily [Cycle 1, Day 1: Predose and 0.5, 1, 1.5, 2, 3, 4, and 8 h postdose; Day 8: Predose and 1.5 h postdose; Day 15: Predose and 1.5 h postdose Cycle 2, Day 1: Predose and 1.5 h postdose]

4. Overall Response Rate (ORR) [Up to 2 years]

   Overall response rate (ORR) was defined as the percentage of participants who achieved a Complete Response (CR) or Partial Response (PR) as assessed by response evaluation criteria in sold tumors (RECIST) v1.1.

5. Overall Survival (OS) [Up to 2 years]

   Overall survival is defined as the interval from first dose date of study drug to death from any cause.

6. Progression Free Survival (PFS) [Up to 2 years]

   Progression free survival is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• The presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

• Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR

• Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin

• Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1

• Prior systemic chemotherapy treatment for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib single agent only)

• Received one prior line of chemotherapy for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + mFOLFOX6 only)

• Adequate organ function defined as follows:

• Hepatic: Total bilirubin ≤ 1.25 x upper limit of normal (ULN) (Arm: idelalisib + nab-paclitaxel ); total bilirubin ≤1.5 x ULN (Arm: single agent idelalisib and Arm: idelalisib + mFOLFOX6); aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT), alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) < 2.5 x ULN, and albumin > 3.0 g/dL

• Hematological: absolute neutrophil count (ANC) > 1,500 cells/cubic millimetre (m^{3), platelet > 100,000 cells/mm}3, hemoglobin > 9.0 grams/decilitre (g/dL)

• Renal: Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) > 30 millilitre (ml)/min as calculated by the Cockcroft-Gault method

• Able to comprehend and willing to sign the written informed consent form

Key Exclusion Criteria:

• Currently or previously treated with biologic, or immunotherapy

• Currently or previously treated with conventional chemotherapy, or other agents for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + nab-paclitaxel only)

• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment

• Known human immunodeficiency viruses (HIV) infection

• History of a concurrent or second malignancy except for 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 enrollment, adequately treated Stage 1 or 2 non-pancreatic cancer currently in complete remission, or any other non-pancreatic cancer that has been in complete remission for ≥ 5 years

• Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (eg, lymphoma, sarcoma), adenocarcinoma originating from the biliary tree or cystadenocarcinoma

• History of serious allergic reaction, including anaphylaxis and toxic epidermal necrolysis

• Presence of peripheral neuropathy ≥ Grade 2 (Arm: idelalisib + nab-paclitaxel and Arm: idelalisib + mFOLFOX6)

• Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg, unstable angina, congestive heart failure [New York Heart Association > Class III]) within 6 months or enrollment

• Known hypersensitivity to idelalisib, its metabolites, or formulation excipients

• Known hypersensitivity to nab-paclitaxel (Arm: idelalisib + nab-paclitaxel), their metabolites, or formulation excipients

• Known hypersensitivity to 5-fluorouracil, leucovorin, or oxaliplatin (Arm: idelalisib

• mFOLFOX6), their metabolites, or formulation excipients

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scottsdale Healthcare Clinical Research Institute	Scottsdale	Arizona	United States	85258
2	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
3	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
4	Georgetown University	Washington	District of Columbia	United States	20007
5	Indiana University Goshen Center for Cancer Care	Goshen	Indiana	United States	46506
6	Dana Farber/ Harvard Cancer Institute	Boston	Massachusetts	United States	02215
7	University of Rochester	Rochester	New York	United States	14642
8	Greenville Hospital System	Greenville	South Carolina	United States	29605
9	Mary Crowley Medical Research Center	Dallas	Texas	United States	75230

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

• Borazanci E, Pishvaian MJ, Nemunaitis J, Weekes C, Huang J, Rajakumaraswamy N. A Phase Ib Study of Single-Agent Idelalisib Followed by Idelalisib in Combination with Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma. Oncologist. 2020 Nov;25(11):e1604-e1613. doi: 10.1634/theoncologist.2020-0321. Epub 2020 Jun 18.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02468557
• Other Study ID Numbers: GS-US-385-1577
• First Posted: Jun 11, 2015
• Last Update Posted: Apr 2, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Adenocarcinoma; Paclitaxel; Idelalisib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in the United States. The first participant was screened on 30 July 2015. The last study visit occurred on 27 April 2016.
Pre-assignment Detail	35 participants were screened. The study was terminated. No participants were enrolled in the Idelalisib (IDL) + nab-paclitaxel or IDL + mFOLFOX [5- fluorouracil (FU), leucovorin and oxaliplatin] groups.

Arm/Group Title	Idelalisib 150 mg
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
Period Title: Overall Study
STARTED	16
COMPLETED	0
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Idelalisib 150 mg
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (10.7)
Sex: Female, Male (Count of Participants)
Female	6 50%
Male	6 50%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Black	1 8.3%
Native Hawaiian or Pacific Islander	0 0%
White	11 91.7%
Other	0 0%
Not Permitted	0 0%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	12 100%
Not Permitted	0 0%

Outcome Measures

1. Primary Outcome

Title	Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
Description	TEAEs were defined as adverse events (AEs) with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the study drug. It also included the AEs that led to premature discontinuation of study drug.
Time Frame	First dose date up to last dose date (Maximum: 8 weeks) plus 30 days

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Idelalisib 150 mg
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
Measure Participants	12
Number [percentage of participants]	100.0 833.3%

2. Primary Outcome

Title	Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
Description	Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post baseline time point, up to and including the date of last dose of study drug plus 30 days. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Severity grade is defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening). The percentage of participants for any post-baseline abnormal laboratory value in the Grade 1-4 category is reported. The term 'hypo' indicates less than the normal count of a parameter and 'hyper' indicates more than the normal count of a parameter.
Time Frame	First dose date up to last dose date (Maximum: 8 weeks) plus 30 days

Outcome Measure Data

Analysis Population Description

Participants in the safety analysis set were analysed.

Arm/Group Title	Idelalisib 150 mg
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
Measure Participants	12
Hemoglobin (Hypo), Hematology	25.0 208.3%
Lymphocytes (Hyper), Hematology	8.3 69.2%
Lymphocytes (Hypo), Hematology	25.0 208.3%
Platelets, Hematology	8.3 69.2%
Alanine Aminotransferase, Chemistry	58.3 485.8%
Albumin, Chemistry	16.7 139.2%
Alkaline Phosphatase, Chemistry	33.3 277.5%
Aspartate Aminotransferase, Chemistry	66.7 555.8%
Bilirubin, Chemistry	16.7 139.2%
Creatinine Clearance, Chemistry	16.7 139.2%
Gamma Glutamyl Transferase, Chemistry	50.0 416.7%
Glucose (Hyper), Chemistry	16.7 139.2%
Sodium (Hypo), Chemistry	25.0 208.3%

3. Primary Outcome

Title	Idelalisib in Combination With Chemotherapy: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Description	Dose limiting toxicities were defined as toxicities experienced during the first 28 days of treatment (Cycle 1) that were judged to be clinically significant and at least possibly related to study treatment.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study, there were no participants enrolled in the Idelalisib Combination arms.

Arm/Group Title	Idelalisib + Nab-paclitaxel	Idelalisib + mFOLFOX6
Arm/Group Description	Participants were to be administered IDL tablets orally twice daily plus nab-paclitaxel administered intravenously on Days 1, 8 and 15 of each 28 day cycle.	Participants were to be administered IDL tablets orally twice daily plus mFOLFOX6 administered intravenously on Days 1 and 15 of each 28 day cycle.
Measure Participants	0	0

4. Secondary Outcome

Title	Change From Baseline in FoxP3+ and Cluster Determinant 8+ (CD8+) Cells From Tumor Tissue Samples as a Measure of Pharmacodynamics Activity
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study no pharmacodynamic testing was performed.

Arm/Group Title	Idelalisib 150 mg	Idelalisib + Nab-paclitaxel	Idelalisib + mFOLFOX6
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.	Participants were to be administered IDL tablets orally twice daily plus nab-paclitaxel administered intravenously on Days 1, 8 and 15 of each 28 day cycle.	Participants were to be administered IDL tablets orally twice daily plus mFOLFOX6 administered intravenously on Days 1 and 15 of each 28 day cycle.
Measure Participants	0	0	0

5. Secondary Outcome

Title	Idelalisib Plasma Concentrations Following Idelalisib 150 mg Twice Daily
Time Frame	Cycle 1, Day 1: Predose and 0.5, 1, 1.5, 2, 3, 4, and 8 hours (h) postdose; Day 8: Predose and 1.5 h postdose; Day 15: Predose and 1.5 h postdose Cycle 2, Day 1: Predose and 1.5 h postdose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) Analysis Set included all participants in the Full Analysis Set who had the necessary baseline and on-study measurements to provide interpretable results for the specific parameters of interest. Due to the early termination of the study, concentration data is reported because there was an insufficient number of participants sampled for PK analysis to generate PK parameters.

Arm/Group Title	Idelalisib 150 mg
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
Measure Participants	12
Cycle 1; Day 1 (Predose)	NA
Cycle 1; Day 1 (0.5 h)	1110
Cycle 1; Day 1 (1 h)	1880
Cycle 1; Day 1 (1.5 h)	1690
Cycle 1; Day 1 (2 h)	1290
Cycle 1; Day 1 (3 h)	795
Cycle 1; Day 1 (4 h)	1540
Cycle 1; Day 1 (8 h)	251
Cycle 1; Day 8 (Predose)	264
Cycle 1; Day 8 (1.5 h)	2050
Cycle 1; Day 15 (Predose)	275
Cycle 1; Day 15 (1.5 h)	1605
Cycle 2; Day 1 (Predose)	178.05
Cycle 2; Day 1 (1.5 h)	2180

6. Secondary Outcome

Title	Idelalisib Metabolite (GS-563117) Plasma Concentrations Following Idelalisib 150 mg Twice Daily
Time Frame	Cycle 1, Day 1: Predose and 0.5, 1, 1.5, 2, 3, 4, and 8 h postdose; Day 8: Predose and 1.5 h postdose; Day 15: Predose and 1.5 h postdose Cycle 2, Day 1: Predose and 1.5 h postdose

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analysed. Due to the early termination of the study, concentration data is reported because there was an insufficient number of participants sampled for PK analysis to generate PK parameters.

Arm/Group Title	Idelalisib 150 mg
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
Measure Participants	12
Cycle 1; Day 1 (Predose)	NA
Cycle 1; Day 1 (0.5 h)	173
Cycle 1; Day 1 (1 h)	1220
Cycle 1; Day 1 (1.5 h)	1070
Cycle 1; Day 1 (2 h)	1700
Cycle 1; Day 1 (3 h)	1580
Cycle 1; Day 1 (4 h)	1370
Cycle 1; Day 1 (8 h)	632
Cycle 1; Day 8 (Predose)	2175
Cycle 1; Day 8 (1.5 h)	2775
Cycle 1; Day 15 (Predose)	2130
Cycle 1; Day 15 (1.5 h)	2890
Cycle 2; Day 1 (Predose)	1046.5
Cycle 2; Day 1 (1.5 h)	1405

7. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Overall response rate (ORR) was defined as the percentage of participants who achieved a Complete Response (CR) or Partial Response (PR) as assessed by response evaluation criteria in sold tumors (RECIST) v1.1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Due to early study termination, the prespecified efficacy analyses were not conducted.

Arm/Group Title	Idelalisib 150 mg	Idelalisib + Nab-paclitaxel	Idelalisib + mFOLFOX6
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.	Participants were to be administered IDL tablets orally twice daily plus nab-paclitaxel administered intravenously on Days 1, 8 and 15 of each 28 day cycle.	Participants were to be administered IDL tablets orally twice daily plus mFOLFOX6 administered intravenously on Days 1 and 15 of each 28 day cycle.
Measure Participants	0	0	0

8. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the interval from first dose date of study drug to death from any cause.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Due to early study termination, the prespecified efficacy analyses were not conducted.

Arm/Group Title	Idelalisib 150 mg	Idelalisib + Nab-paclitaxel	Idelalisib + mFOLFOX6
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.	Participants were to be administered IDL tablets orally twice daily plus nab-paclitaxel administered intravenously on Days 1, 8 and 15 of each 28 day cycle.	Participants were to be administered IDL tablets orally twice daily plus mFOLFOX6 administered intravenously on Days 1 and 15 of each 28 day cycle.
Measure Participants	0	0	0

9. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression free survival is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Due to early study termination, the prespecified efficacy analyses were not conducted.

Arm/Group Title	Idelalisib 150 mg	Idelalisib + Nab-paclitaxel	Idelalisib + mFOLFOX6
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.	Participants were to be administered IDL tablets orally twice daily plus nab-paclitaxel administered intravenously on Days 1, 8 and 15 of each 28 day cycle.	Participants were to be administered IDL tablets orally twice daily plus mFOLFOX6 administered intravenously on Days 1 and 15 of each 28 day cycle.
Measure Participants	0	0	0

Adverse Events

Time Frame	Adverse Events: First dose date up to last dose date (Maximum: 8 weeks) plus 30 days All-cause mortality: First dose date up to study termination (approximately 39 weeks)
Adverse Event Reporting Description	The Safety Analysis Set included all participants who received at least 1 dose of study drug.
Arm/Group Title	Idelalisib 150 mg
Arm/Group Description	Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
All Cause Mortality
	Idelalisib 150 mg
	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)
Serious Adverse Events
	Idelalisib 150 mg
	Affected / at Risk (%)	# Events
Total	3/12 (25%)
Blood and lymphatic system disorders
Coagulopathy	1/12 (8.3%)
Gastrointestinal disorders
Small intestinal obstruction	1/12 (8.3%)
Upper gastrointestinal haemorrhage	1/12 (8.3%)
General disorders
Pyrexia	1/12 (8.3%)
Investigations
Alanine aminotransferase increased	1/12 (8.3%)
Aspartate aminotransferase increased	1/12 (8.3%)
Metabolism and nutrition disorders
Dehydration	1/12 (8.3%)
Diabetes mellitus inadequate control	1/12 (8.3%)
Renal and urinary disorders
Acute kidney injury	1/12 (8.3%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Idelalisib 150 mg
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Gastrointestinal disorders
Abdominal discomfort	1/12 (8.3%)
Abdominal pain	2/12 (16.7%)
Abdominal pain upper	1/12 (8.3%)
Ascites	1/12 (8.3%)
Constipation	2/12 (16.7%)
Diarrhoea	1/12 (8.3%)
Nausea	1/12 (8.3%)
Rectal spasm	1/12 (8.3%)
Vomiting	2/12 (16.7%)
General disorders
Chills	2/12 (16.7%)
Fatigue	1/12 (8.3%)
Pyrexia	5/12 (41.7%)
Xerosis	1/12 (8.3%)
Infections and infestations
Bacteraemia	1/12 (8.3%)
Investigations
Alanine aminotransferase increased	3/12 (25%)
Aspartate aminotransferase increased	4/12 (33.3%)
Blood alkaline phosphatase increased	1/12 (8.3%)
Blood bilirubin increased	1/12 (8.3%)
Weight decreased	1/12 (8.3%)
Metabolism and nutrition disorders
Decreased appetite	1/12 (8.3%)
Hyponatraemia	1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)
Muscular weakness	1/12 (8.3%)
Nervous system disorders
Aphasia	1/12 (8.3%)
Dizziness	1/12 (8.3%)
Hypoaesthesia	1/12 (8.3%)
Paraesthesia	1/12 (8.3%)
Psychiatric disorders
Insomnia	2/12 (16.7%)
Renal and urinary disorders
Chromaturia	1/12 (8.3%)
Haematuria	2/12 (16.7%)
Urinary tract obstruction	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/12 (8.3%)
Haemoptysis	1/12 (8.3%)
Skin and subcutaneous tissue disorders
Onycholysis	1/12 (8.3%)
Pruritus	1/12 (8.3%)
Rash	2/12 (16.7%)
Rash macular	1/12 (8.3%)
Rash maculo-papular	2/12 (16.7%)
Vascular disorders
Hypertension	1/12 (8.3%)

Limitations/Caveats

Due to the early termination of the study, the prespecified efficacy, pharmacodynamic, and pharmacokinetic analysis for PK parameters were not conducted.

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