Idelalisib in Combination With Rituximab for Previously Untreated Follicular Lymphoma and Small Lymphocytic Lymphoma

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02258529
• Collaborator: (none)
• Enrollment: 10
• Locations: 6
• Arm: 1
• Actual Duration (Months): 7.6
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the overall response rate (ORR) and complete response (CR) rate to treatment with idelalisib in combination with rituximab in previously untreated adults with follicular lymphoma (FL) or small lymphocytic lymphoma (SLL).

An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated those studies in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA). All front-line studies of idelalisib, including this study, were also terminated.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma; Small Lymphocytic Lymphoma	Drug: Idelalisib; Biological: Rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Single Arm Study Evaluating the Safety and Efficacy of Idelalisib in Combination With Rituximab for Previously Untreated Follicular Lymphoma and Small Lymphocytic Lymphoma
• Actual Study Start Date: Sep 14, 2015
• Actual Primary Completion Date: Apr 12, 2016
• Actual Study Completion Date: May 3, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Idelalisib + rituximab Idelalisib + rituximab for up to 104 weeks	Drug: Idelalisib; 150 tablets administered orally twice daily; Other Names: Zydelig® GS-1101 ; Biological: Rituximab; 375 mg/m^2 administered intravenously (weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100); Other Names: Rituxan® MabThera®

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate []

   Overall response rate (ORR) was defined as the proportion of participants who achieve a confirmed complete or partial response during idelalisib treatment. ORR was to be assessed by an independent review committee (IRC).

Secondary Outcome Measures

1. Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death [Up to 24 weeks plus 30 days]

2. Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings [Up to 24 weeks plus 30 days]

   The rate of Grade ≥ 3 transaminase elevations was defined as the number of participants with any Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations.

3. Idelalisib Trough and Peak Plasma Concentrations [Predose and 1.5 hour postdose at Weeks 2, 4, and 12]

4. Time to Response []

   Time to response was defined as the the interval from the start of idelalisib treatment to the first documentation of complete or partial response.

5. Duration of Response []

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

6. Progression-Free Survival []

   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 or death from any cause.

7. Overall Survival []

   Overall survival was defined as the interval from enrollment to death from any cause.

8. Changes in Health-Related Quality of Life []

   Changes in health-related quality of life was to be reported by participants using the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) questionnaire.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Histologically confirmed diagnosis of B-cell lymphoma

• No previous systemic treatment for lymphoma

• Subject demonstrates need for treatment for lymphoma

• Ann-Arbor Stage 2 (noncontiguous), 3, or 4 disease

• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy

• Adequate performance status

• Required baseline laboratory data within protocol-specified parameters

Key Exclusion Criteria:

• Known history of transformed lymphoma or diffuse large cell lymphoid malignancy

• Known history of, or clinically apparent, central nervous system (CNS) lymphoma or leptomeningeal lymphoma

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

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

• Ongoing inflammatory bowel disease

• Known human immunodeficiency virus (HIV) infection

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

• Ongoing immunosuppressive therapy, including systemic corticosteroids (> 10 mg prednisone or equivalent/day) with the exception of the use of topical, enteric, or inhaled corticosteroids as therapy for comorbid conditions and systemic steroids for autoimmune anemia and/or thrombocytopenia

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Shores Medical Group	Long Beach	California	United States	90813
2	Florida Cancer Specialists	Fort Myers	Florida	United States	33916
3	St. Agnes Hospital	Baltimore	Maryland	United States	21229
4	Prarie Lakes Health Care Systems, Inc.	Watertown	South Dakota	United States	57201
5	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
6	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405

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: NCT02258529
• Other Study ID Numbers: GS-US-313-1414
• First Posted: Oct 7, 2014
• Last Update Posted: May 14, 2019
• Last Verified: Apr 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: Cancer; Indolent Non-Hodgkin Lymphoma; FL; SLL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; 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 14 September 2015. The last study visit occurred on 03 May 2016.
Pre-assignment Detail	20 participants were screened.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib (Zydelig®) 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Period Title: Overall Study
STARTED	10
COMPLETED	0
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69 (11.7)
Sex: Female, Male (Count of Participants)
Female	6 60%
Male	4 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Overall response rate (ORR) was defined as the proportion of participants who achieve a confirmed complete or partial response during idelalisib treatment. ORR was to be assessed by an independent review committee (IRC).

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	0

2. Secondary Outcome

Title	Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death
Time Frame	Up to 24 weeks plus 30 days

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Analysis Set: all participants who received at least 1 dose of study drug.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	10
Any AE	90.0 900%
Any SAEs	30.0 300%
Any AE Leading to Idelalisib Interruption	60.0 600%
Any AE Leading to Idelalisib Dose Reduction	30.0 300%
Any AE Leading to Premature Discontinuation of IDL	10.0 100%
Any AE Leading to Death	0 0%

3. Secondary Outcome

Title	Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings
Description	The rate of Grade ≥ 3 transaminase elevations was defined as the number of participants with any Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations.
Time Frame	Up to 24 weeks plus 30 days

Outcome Measure Data

Analysis Population Description

ITT Analysis Set: all participants who received at least 1 dose of study drug.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	10
Any Grade 3 or 4 ALT Elevation	40.0 400%
Any Grade 3 or 4 AST Elevation	10.0 100%

4. Secondary Outcome

Title	Idelalisib Trough and Peak Plasma Concentrations
Time Frame	Predose and 1.5 hour postdose at Weeks 2, 4, and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	9
Week 2 predose	216.2 (161.73)
Week 2 1.5 hours postdose	2240.0 (880.03)
Week 4 predose	347.4 (365.57)
Week 4 1.5 hours postdose	2084.3 (1346.26)
Week 12 predose	290.5 (373.08)
Week 12 1.5 hours postdose	1313.1 (1474.87)

5. Secondary Outcome

Title	Time to Response
Description	Time to response was defined as the the interval from the start of idelalisib treatment to the first documentation of complete or partial response.

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	0

6. Secondary Outcome

Title	Duration of Response
Description	Duration of response (DOR) was defined as the interval from the first documentation of complete response or partial response to the earlier of the first documentation of disease progression or death from any cause.

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	0

7. 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 or death from any cause.

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	0

8. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the interval from enrollment to death from any cause.

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study, efficacy data were not mature for all participants, and therefore the prespecified analyses were not conducted.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	0

9. Secondary Outcome

Title	Changes in Health-Related Quality of Life
Description	Changes in health-related quality of life was to be reported by participants using the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) questionnaire.

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study, data were not available for all participants, and therefore this prespecified analysis was not conducted.

Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Measure Participants	0

Adverse Events

Time Frame	Baseline up to the last dose date plus 30 days (maximum: 24.1 weeks)
Adverse Event Reporting Description	ITT Analysis Set: all participants who received at least 1 dose of study drug.
Arm/Group Title	Idelalisib + Rituximab
Arm/Group Description	Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
All Cause Mortality
	Idelalisib + Rituximab
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Idelalisib + Rituximab
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
General disorders
Oedema peripheral	1/10 (10%)
Infections and infestations
Sepsis	1/10 (10%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/10 (10%)
Nervous system disorders
Trigeminal neuralgia	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/10 (10%)
Other (Not Including Serious) Adverse Events
	Idelalisib + Rituximab
	Affected / at Risk (%)	# Events
Total	9/10 (90%)
Blood and lymphatic system disorders
Neutropenia	3/10 (30%)
Pancytopenia	1/10 (10%)
Cardiac disorders
Palpitations	1/10 (10%)
Sinus tachycardia	1/10 (10%)
Ear and labyrinth disorders
Ear pruritus	1/10 (10%)
Gastrointestinal disorders
Abdominal distension	1/10 (10%)
Abdominal pain	1/10 (10%)
Constipation	1/10 (10%)
Diarrhoea	3/10 (30%)
Duodenal ulcer	1/10 (10%)
Duodenitis	1/10 (10%)
Gastritis	1/10 (10%)
Hiatus hernia	1/10 (10%)
Lip dry	1/10 (10%)
Nausea	2/10 (20%)
Oesophagitis	1/10 (10%)
Stomatitis	1/10 (10%)
Vomiting	3/10 (30%)
General disorders
Asthenia	1/10 (10%)
Chills	2/10 (20%)
Fatigue	3/10 (30%)
Mucosal inflammation	1/10 (10%)
Oedema peripheral	2/10 (20%)
Peripheral swelling	1/10 (10%)
Pyrexia	2/10 (20%)
Hepatobiliary disorders
Hepatic steatosis	1/10 (10%)
Hepatitis acute	1/10 (10%)
Periportal oedema	1/10 (10%)
Immune system disorders
Hypersensitivity	1/10 (10%)
Infections and infestations
Bronchitis	1/10 (10%)
Oral candidiasis	1/10 (10%)
Urinary tract infection	1/10 (10%)
Injury, poisoning and procedural complications
Fall	1/10 (10%)
Infusion related reaction	4/10 (40%)
Investigations
Alanine aminotransferase increased	5/10 (50%)
Aspartate aminotransferase increased	5/10 (50%)
Blood cholesterol increased	1/10 (10%)
Liver function test increased	2/10 (20%)
Lymphocyte count decreased	1/10 (10%)
Neutrophil count decreased	1/10 (10%)
Platelet count decreased	1/10 (10%)
Weight decreased	1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	1/10 (10%)
Hypertriglyceridaemia	1/10 (10%)
Hyperuricaemia	1/10 (10%)
Hypophosphataemia	1/10 (10%)
Lactic acidosis	1/10 (10%)
Malnutrition	1/10 (10%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/10 (10%)
Muscular weakness	1/10 (10%)
Musculoskeletal chest pain	1/10 (10%)
Pain in extremity	2/10 (20%)
Nervous system disorders
Dementia	1/10 (10%)
Dizziness	1/10 (10%)
Dysarthria	1/10 (10%)
Headache	1/10 (10%)
Hypoaesthesia	1/10 (10%)
Neuropathy peripheral	1/10 (10%)
Paraesthesia	1/10 (10%)
Transient ischaemic attack	1/10 (10%)
Psychiatric disorders
Acute psychosis	1/10 (10%)
Delirium	1/10 (10%)
Insomnia	1/10 (10%)
Renal and urinary disorders
Acute kidney injury	3/10 (30%)
Respiratory, thoracic and mediastinal disorders
Cough	1/10 (10%)
Dysphonia	1/10 (10%)
Dyspnoea	2/10 (20%)
Dyspnoea exertional	1/10 (10%)
Hypoxia	1/10 (10%)
Oropharyngeal pain	1/10 (10%)
Pneumonitis	1/10 (10%)
Throat irritation	1/10 (10%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/10 (10%)
Ecchymosis	1/10 (10%)
Hyperhidrosis	1/10 (10%)
Night sweats	1/10 (10%)
Rash	3/10 (30%)
Rash maculo-papular	3/10 (30%)
Urticaria	1/10 (10%)
Vascular disorders
Flushing	2/10 (20%)

Limitations/Caveats

Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses 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