Trial Outcomes & Findings for Safety and Efficacy of Idelalisib in Relapsed or Refractory Hodgkin Lymphoma (NCT NCT01393106)
NCT ID: NCT01393106
Last Updated: 2018-11-19
Results Overview
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 proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator. * 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.
COMPLETED
PHASE2
25 participants
Up to Week 110
2018-11-19
Participant Flow
Participants were enrolled at study sites in the United States. The first participant was screened on 15 September 2011. The last study visit occurred on 28 August 2014.
32 participants were screened.
Participant milestones
| Measure |
Idelalisib
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Idelalisib
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
Baseline Characteristics
Safety and Efficacy of Idelalisib in Relapsed or Refractory Hodgkin Lymphoma
Baseline characteristics by cohort
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
43 years
STANDARD_DEVIATION 16.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
19 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
22 participants
n=5 Participants
|
|
Time Since Diagnosis (years)
|
3.9 years
STANDARD_DEVIATION 4.26 • n=5 Participants
|
|
Classical Hodgkin Lymphoma Pathologic Subtype
Nodular Sclerosis
|
23 participants
n=5 Participants
|
|
Classical Hodgkin Lymphoma Pathologic Subtype
Lymphocyte Rich
|
2 participants
n=5 Participants
|
|
Disease Stage at Screening
Stage I
|
1 participants
n=5 Participants
|
|
Disease Stage at Screening
Stage II
|
8 participants
n=5 Participants
|
|
Disease Stage at Screening
Stage III
|
6 participants
n=5 Participants
|
|
Disease Stage at Screening
Stage IV
|
10 participants
n=5 Participants
|
|
Karnofsky Performance Status
|
83 units on a scale
STANDARD_DEVIATION 7.1 • n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Week 110Population: Intent-to-treat (ITT) Analysis Set: participants who received at least one dose of study drug.
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 proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator. * 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.
Outcome measures
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Overall Response Rate
|
20.0 percentage of participants
Interval 6.8 to 40.7
|
SECONDARY outcome
Timeframe: Up to Week 110Population: Responding Analysis Set: participants who achieved a best response of CR or PR.
Duration of response (DOR) was defined as the interval from the first documentation of PR or CR to the earlier of the first documentation of disease progression or death from any cause.
Outcome measures
| Measure |
Idelalisib
n=5 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Duration of Response
|
8.4 months
Interval 1.8 to
Not reached
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 48, and up to Week 110Population: ITT Analysis Set
Outcome measures
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of Target Lymph Nodes as Documented Radiographically
Percent Change at Week 8 (n = 24)
|
-14.1 percent change in SPD
Interval -73.1 to 112.5
|
|
Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of Target Lymph Nodes as Documented Radiographically
Percent Change at Week 48 (n = 5)
|
-45.9 percent change in SPD
Interval -92.6 to 7.8
|
|
Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of Target Lymph Nodes as Documented Radiographically
Best Percent Change from Baseline (n = 24)
|
-24.1 percent change in SPD
Interval -92.6 to 112.5
|
SECONDARY outcome
Timeframe: Up to Week 110Population: An analysis of changes in FDG uptake by the tumor was not conducted due to unavailability of lymph node biopsy samples.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 110Population: Responding Analysis Set
Time to response (TTR) was defined as the interval from the start of idelalisib treatment to the first documentation of CR or PR.
Outcome measures
| Measure |
Idelalisib
n=5 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Time to Response
|
2.0 months
Interval 1.9 to 16.8
|
SECONDARY outcome
Timeframe: Up to Week 110Population: ITT Analysis Set
Overall survival was defined as the time from start of idelalisib treatment to death from any cause.
Outcome measures
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Overall Survival
|
19.8 months
Interval 12.3 to
Not reached
|
SECONDARY outcome
Timeframe: Up to Week 110Population: ITT Analysis Set
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 measures
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Progression Free Survival
|
2.3 months
Interval 1.8 to 3.7
|
SECONDARY outcome
Timeframe: Up to Week 110Population: No data are presented because time to treatment failure data were not collected.
Time to treatment failure (TTF) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression, the permanent cessation of idelalisib therapy due to an adverse event, or death from any cause.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and up to Week 110Population: FACT-Lym Evaluable Analysis Set: participants who had sufficient baseline and on-study measurements to provide interpretable results for this endpoint.
Change in health-related quality of life was reported by participants using the FACT-Lym questionnaire assessment tool. Results are presented as the mean (SD) best change from baseline in FACT-Lym total score, which was defined as the highest change score (improvement) after baseline. The FACT-Lym total score is on a scale from 0-168, with higher scores associated with a better quality of life.
Outcome measures
| Measure |
Idelalisib
n=20 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Changes in Health-related Quality of Life as Reported Using the Functional Assessment of Cancer Therapy: Lymphoma (FACT-Lym) Questionnaire
|
5.1 units on a scale
Standard Deviation 7.24
|
SECONDARY outcome
Timeframe: Baseline and up to Week 110Population: Participants in the ITT Analysis Set with available data were analyzed.
Changes in performance status were assessed using the Karnofsky performance criteria for participants ≥ 16 years of age and the Lansky performance criteria for participants \< 16 years of age. Since there were no participants \< 16 years of age, only the Karnofsky performance criteria were used. 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 classifies patients 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.
Outcome measures
| Measure |
Idelalisib
n=7 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Changes in Performance Status as Documented Using the Karnofsky Performance Criteria for Participants ≥ 16 Years of Age and the Lansky Performance Criteria for Participants < 16 Years of Age
Best Change
|
6 units on a scale
Standard Deviation 5.3
|
|
Changes in Performance Status as Documented Using the Karnofsky Performance Criteria for Participants ≥ 16 Years of Age and the Lansky Performance Criteria for Participants < 16 Years of Age
Worst Change
|
-1 units on a scale
Standard Deviation 6.9
|
SECONDARY outcome
Timeframe: Up to Week 110Population: This analysis was not conducted due to discrepancies with the transfer of samples.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 110Population: ITT Analysis Set
The overall safety of idelalisib was assessed as the percentage of participants experiencing adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib), clinically significant abnormal electrocardiograms (ECG), and laboratory abnormalities. "Clinically significant" abnormalities in ECG were as determined by the investigator.
Outcome measures
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Overall Safety Profile of Idelalisib
AE related to idelalisib
|
76.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Any AE
|
96.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Serious AE
|
36.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Grade ≥ 3 AE
|
48.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
AE leading to permanent drug discontinuation
|
8.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Clinically significant abnormal ECG at Week 16
|
0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Grade 3 or 4 hemoglobin
|
4.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Grade 3 or 4 neutrophils
|
8.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Grade 3 or 4 platelets
|
4.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Grade 3 or 4 alanine aminotransferase
|
20.0 percentage of participants
|
|
Overall Safety Profile of Idelalisib
Grade 3 or 4 aspartate aminotransferase
|
16.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 110Population: ITT Analysis Set
Outcome measures
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Compliance With Study Drug Dosing as Assessed by Accounting for Used and Unused Drug
Number of doses dispensed
|
463 number of doses
Standard Deviation 462.3
|
|
Compliance With Study Drug Dosing as Assessed by Accounting for Used and Unused Drug
Number of doses taken
|
329 number of doses
Standard Deviation 321.1
|
SECONDARY outcome
Timeframe: Predose and 1.5 hours postdose at Week 4Population: Participants in the ITT Analysis Set with available data were analyzed.
Plasma samples were collected predose (trough) and 1.5 hours postdose (peak). The minimum and maximum value among participants sampled at each time point are presented. Results of less than the lower limit of quantitation (ie, 5 ng/mL) were treated as zero prior to the achievement of the first quantifiable concentration and as missing otherwise.
Outcome measures
| Measure |
Idelalisib
n=25 Participants
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Idelalisib Trough and Peak Plasma Concentration at Week 4
Trough - minimum (n = 20)
|
142 ng/mL
|
|
Idelalisib Trough and Peak Plasma Concentration at Week 4
Trough - maximum (n = 20)
|
2120.0 ng/mL
|
|
Idelalisib Trough and Peak Plasma Concentration at Week 4
Peak - minimum (n = 22)
|
90.2 ng/mL
|
|
Idelalisib Trough and Peak Plasma Concentration at Week 4
Peak - maximum (n = 22)
|
8570.0 ng/mL
|
Adverse Events
Idelalisib
Serious adverse events
| Measure |
Idelalisib
n=25 participants at risk
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Colitis
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Vomiting
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
General disorders
Pyrexia
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Infections and infestations
Herpes zoster
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Infections and infestations
Lung infection
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Infections and infestations
Pneumonia
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Infections and infestations
Skin infection
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Investigations
Platelet count decreased
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Surgical and medical procedures
Hospitalisation
|
4.0%
1/25 • Up to Week 110
ITT Analysis Set
|
Other adverse events
| Measure |
Idelalisib
n=25 participants at risk
Idelalisib up to 300 mg (75, 100, or 150 mg tablets) administered orally twice daily until tumor progression or development of unacceptable toxicity.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
12.0%
3/25 • Up to Week 110
ITT Analysis Set
|
|
Blood and lymphatic system disorders
Leukopenia
|
16.0%
4/25 • Up to Week 110
ITT Analysis Set
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.0%
4/25 • Up to Week 110
ITT Analysis Set
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.0%
4/25 • Up to Week 110
ITT Analysis Set
|
|
Cardiac disorders
Tachycardia
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Constipation
|
24.0%
6/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Diarrhoea
|
12.0%
3/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Dyspepsia
|
16.0%
4/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
16.0%
4/25 • Up to Week 110
ITT Analysis Set
|
|
Gastrointestinal disorders
Vomiting
|
24.0%
6/25 • Up to Week 110
ITT Analysis Set
|
|
General disorders
Chills
|
20.0%
5/25 • Up to Week 110
ITT Analysis Set
|
|
General disorders
Fatigue
|
32.0%
8/25 • Up to Week 110
ITT Analysis Set
|
|
General disorders
Pain
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
General disorders
Pyrexia
|
24.0%
6/25 • Up to Week 110
ITT Analysis Set
|
|
Infections and infestations
Upper respiratory tract infection
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Injury, poisoning and procedural complications
Fall
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
5/25 • Up to Week 110
ITT Analysis Set
|
|
Investigations
Aspartate aminotransferase increased
|
24.0%
6/25 • Up to Week 110
ITT Analysis Set
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
16.0%
4/25 • Up to Week 110
ITT Analysis Set
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Nervous system disorders
Memory impairment
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Nervous system disorders
Neuropathy peripheral
|
12.0%
3/25 • Up to Week 110
ITT Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
5/25 • Up to Week 110
ITT Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
12.0%
3/25 • Up to Week 110
ITT Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.0%
3/25 • Up to Week 110
ITT Analysis Set
|
|
Vascular disorders
Hypertension
|
8.0%
2/25 • Up to Week 110
ITT Analysis Set
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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
- Publication restrictions are in place
Restriction type: OTHER