Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT01980875
Collaborator
(none)
57
18
3
12.7
3.2
0.2
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the effects of idelalisib with obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).
An increased rate of deaths and serious adverse events (SAEs) among participants with front-line 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 |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
57 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Safety Run-In Phase: Single Group; Randomized Phase: ParallelSafety Run-In Phase: Single Group; Randomized Phase: Parallel
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
Actual Study Start Date
:
Apr 21, 2015
Actual Primary Completion Date
:
May 13, 2016
Actual Study Completion Date
:
May 13, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Safety Run-In: Idelalisib+obinutuzumab Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Following 4 weeks of treatment, safety data will be reviewed by an independent data monitoring committee (DMC). If acceptable tolerability is observed, the randomized portion of the study will begin. |
Drug: Idelalisib
150 mg tablet administered orally twice daily
Other Names:
Drug: Obinutuzumab
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
|
| Experimental: Randomized: Idelalisib+obinutuzumab Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. |
Drug: Idelalisib
150 mg tablet administered orally twice daily
Other Names:
Drug: Obinutuzumab
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
|
| Active Comparator: Randomized: Obinutuzumab+chlorambucil Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks. |
Drug: Chlorambucil
2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses
Drug: Obinutuzumab
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival [Up to 11 months]
Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone. PFS was to be assessed by an independent review committee (IRC).
Secondary Outcome Measures
- Overall Response Rate [Up to 11 months]
Overall response rate (ORR) is defined as the proportion of participants who achieve a confirmed complete or partial response. ORR was to be assessed by an IRC.
- Nodal Response Rate [Up to 11 months]
Nodal response rate is defined as the proportion of participants who achieve a 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Nodal response rate was to be assessed by an IRC.
- Complete Response Rate [Up to 11 months]
Complete response rate is defined as the proportion of participants who achieve a confirmed complete response. Complete response rate was to be assessed by an IRC.
- Overall Survival [Up to 11 months]
Overall survival is defined as the interval from randomization to death from any cause. Overall survival was to be assessed by an IRC.
- Minimal Residual Disease Negativity Rate at Week 36 [Up to 11 months]
Minimal residual disease (MRD) negativity rate is defined as the proportion of participants with MRD < 10^-4 assessed by flow cytometry in bone marrow at Week 36 after therapy initiation. For participants receiving the final dose of obinutuzumab after the original scheduled date, the MRD assessment was performed no less than 12 weeks after the last dose of obinutuzumab. MRD negativity rate was to be assessed by an IRC.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
- Not a candidate for fludarabine therapy based on either:
-
creatinine clearance < 70 mL/min, or
-
Cumulative Illness Rating Scale score > 6, by assessment of the investigator
-
Diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
-
No prior therapy for CLL other than corticosteroids for disease complications.
-
CLL that warrants treatment
-
Presence of measurable lymphadenopathy
-
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
Key Exclusion Criteria:
-
Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
-
Known presence of myelodysplastic syndrome
-
Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization
-
Ongoing liver injury
-
Ongoing drug-induced pneumonitis
-
Ongoing inflammatory bowel disease
-
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
-
Ongoing immunosuppressive therapy other than corticosteroids
-
Concurrent participation in another therapeutic clinical trial
-
Undergone major surgery within 30 days prior to randomization
-
Known hypersensitivity or intolerance to any of the active substances or excipients in the formulations for idelalisib, obinutuzumab, or chlorambucil
-
History of non-infectious pneumonitis
-
Received last dose of study drug on another therapeutic clinical trial within 30 days prior to randomization
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sansum Clinic | Santa Barbara | California | United States | 93105 |
| 2 | UCLA Jonsson Comprehensive Cancer Center | Santa Monica | California | United States | 90404 |
| 3 | Innovative Clinical Research Institute | Whittier | California | United States | 90603 |
| 4 | Cancer Center of Central Connecticut | Southington | Connecticut | United States | 06489 |
| 5 | Gabrail Cancer Center Research | Canton | Ohio | United States | 44718 |
| 6 | Saint Francis Cancer Center | Greenville | South Carolina | United States | 29607 |
| 7 | St Vincent Hospital, Sydney | Darlinghurst | New South Wales | Australia | 2010 |
| 8 | UZ Ghent- hematology | Ghent | Belgium | 9000 | |
| 9 | Royal Victoria Regional Health Centre - Simcoe Musk | Barrie | Ontario | Canada | L4M 6M2 |
| 10 | Centre Hospitalier du Mans | Le Mans | France | 72037 | |
| 11 | Centre Hospitalier de Perpignan | Perpignan Cedex 9 | France | 66046-BP 49954 | |
| 12 | Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej | Brzozow | Podkarpackie | Poland | 36-200 |
| 13 | Malopolskie Centrum Medyczne s.c. | Krakow | Poland | 30-510 | |
| 14 | Wojewódzki Szpital Specjalistyczny w Legnicy | Legnica | Poland | 59-220 | |
| 15 | Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego | Lodz | Poland | 93-510 | |
| 16 | Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii | Olsztyn | Poland | 10-228 | |
| 17 | Hospital Universitario de Salamanca | Salamanca | Spain | 37007 | |
| 18 | East Kent Hospitals University NHS Foundation Trust | Canterbury | Kent | United Kingdom | CT1 3NG |
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:
NCT01980875
Other Study ID Numbers:
- GS-US-312-0118
- 2013-004551-20
First Posted:
Nov 11, 2013
Last Update Posted:
Nov 19, 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
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in Australia, Europe, and North America. The first participant was screened on 21 April 2015. The last study visit occurred on 13 May 2016. |
|---|---|
| Pre-assignment Detail | 80 participants were screened. |
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil |
|---|---|---|---|
| Arm/Group Description | Idelalisib (Zydelig®) 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks |
| Period Title: Overall Study | |||
| STARTED | 8 | 25 | 24 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 8 | 25 | 24 |
Baseline Characteristics
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil | Total |
|---|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Total of all reporting groups |
| Overall Participants | 8 | 25 | 24 | 57 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
67.1
(8.10)
|
72.2
(8.23)
|
71.1
(6.84)
|
71.1
(7.70)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
37.5%
|
8
32%
|
9
37.5%
|
20
35.1%
|
| Male |
5
62.5%
|
17
68%
|
15
62.5%
|
37
64.9%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Black or African American |
1
12.5%
|
0
0%
|
0
0%
|
1
1.8%
|
| White |
7
87.5%
|
22
88%
|
21
87.5%
|
50
87.7%
|
| Other |
0
0%
|
1
4%
|
0
0%
|
1
1.8%
|
| Not Permitted |
0
0%
|
2
8%
|
3
12.5%
|
5
8.8%
|
| Region of Enrollment (participants) [Number] | ||||
| Canada |
1
12.5%
|
1
4%
|
0
0%
|
2
3.5%
|
| Belgium |
0
0%
|
1
4%
|
1
4.2%
|
2
3.5%
|
| United States |
5
62.5%
|
3
12%
|
4
16.7%
|
12
21.1%
|
| Poland |
2
25%
|
14
56%
|
12
50%
|
28
49.1%
|
| United Kingdom |
0
0%
|
1
4%
|
2
8.3%
|
3
5.3%
|
| France |
0
0%
|
3
12%
|
2
8.3%
|
5
8.8%
|
| Australia |
0
0%
|
1
4%
|
3
12.5%
|
4
7%
|
| Spain |
0
0%
|
1
4%
|
0
0%
|
1
1.8%
|
| Rai Stage (Count of Participants) | ||||
| Stage I-II |
3
37.5%
|
11
44%
|
9
37.5%
|
23
40.4%
|
| Stage III-IV |
5
62.5%
|
14
56%
|
15
62.5%
|
34
59.6%
|
| IgHV Mutation (Count of Participants) | ||||
| Unmutated |
5
62.5%
|
16
64%
|
17
70.8%
|
38
66.7%
|
| Mutated |
3
37.5%
|
9
36%
|
7
29.2%
|
19
33.3%
|
| 17p Deletion in CLL Cells (Count of Participants) | ||||
| Present |
0
0%
|
3
12%
|
3
12.5%
|
6
10.5%
|
| Absent |
8
100%
|
22
88%
|
21
87.5%
|
51
89.5%
|
Outcome Measures
| Title | Progression-Free Survival |
|---|---|
| Description | Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone. PFS was to be assessed by an independent review committee (IRC). |
| Time Frame | Up to 11 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant. |
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil |
|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks |
| Measure Participants | 0 | 0 | 0 |
| Title | Overall Response Rate |
|---|---|
| Description | Overall response rate (ORR) is defined as the proportion of participants who achieve a confirmed complete or partial response. ORR was to be assessed by an IRC. |
| Time Frame | Up to 11 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant. |
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil |
|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks |
| Measure Participants | 0 | 0 | 0 |
| Title | Nodal Response Rate |
|---|---|
| Description | Nodal response rate is defined as the proportion of participants who achieve a 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Nodal response rate was to be assessed by an IRC. |
| Time Frame | Up to 11 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant. |
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil |
|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks |
| Measure Participants | 0 | 0 | 0 |
| Title | Complete Response Rate |
|---|---|
| Description | Complete response rate is defined as the proportion of participants who achieve a confirmed complete response. Complete response rate was to be assessed by an IRC. |
| Time Frame | Up to 11 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant. |
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil |
|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks |
| Measure Participants | 0 | 0 | 0 |
| Title | Overall Survival |
|---|---|
| Description | Overall survival is defined as the interval from randomization to death from any cause. Overall survival was to be assessed by an IRC. |
| Time Frame | Up to 11 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant. |
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil |
|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks |
| Measure Participants | 0 | 0 | 0 |
| Title | Minimal Residual Disease Negativity Rate at Week 36 |
|---|---|
| Description | Minimal residual disease (MRD) negativity rate is defined as the proportion of participants with MRD < 10^-4 assessed by flow cytometry in bone marrow at Week 36 after therapy initiation. For participants receiving the final dose of obinutuzumab after the original scheduled date, the MRD assessment was performed no less than 12 weeks after the last dose of obinutuzumab. MRD negativity rate was to be assessed by an IRC. |
| Time Frame | Up to 11 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant. |
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil |
|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | Baseline up to the last dose date plus 30 days (maximum: 12 months) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set: participants who received at least 1 dose of study drug, with treatment group designated according to actual treatment received | |||||
| Arm/Group Title | Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil | |||
| Arm/Group Description | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Idelalisib 150 mg tablet twice daily + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | Chlorambucil 0.5 mg/kg, as 2 mg tablets every other week for a total of 12 doses + obinutuzumab 1000 mg/40 mL intravenously for a total of 8 doses over 21 weeks | |||
All Cause Mortality |
||||||
| Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/24 (0%) | 0/23 (0%) | |||
Serious Adverse Events |
||||||
| Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/8 (25%) | 12/24 (50%) | 8/23 (34.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/8 (0%) | 2/24 (8.3%) | 1/23 (4.3%) | |||
| Febrile neutropenia | 0/8 (0%) | 1/24 (4.2%) | 1/23 (4.3%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Enteritis | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| General disorders | ||||||
| Chills | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Pyrexia | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Secondary immunodeficiency | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Infections and infestations | ||||||
| Bronchitis | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Gastroenteritis | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Herpes zoster | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Lung infection | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Pneumonia | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Pyelonephritis | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Sepsis | 0/8 (0%) | 1/24 (4.2%) | 1/23 (4.3%) | |||
| Upper respiratory tract infection | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Infusion related reaction | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Tumour lysis syndrome | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Richter's syndrome | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Nervous system disorders | ||||||
| Leukoencephalopathy | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Pneumonitis | 0/8 (0%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 0/8 (0%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/8 (0%) | 0/24 (0%) | 1/23 (4.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Safety Run-In: Idelalisib+Obinutuzumab | Randomized: Idelalisib+Obinutuzumab | Randomized: Obinutuzumab+Chlorambucil | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/8 (100%) | 19/24 (79.2%) | 17/23 (73.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/8 (25%) | 6/24 (25%) | 2/23 (8.7%) | |||
| Neutropenia | 4/8 (50%) | 6/24 (25%) | 9/23 (39.1%) | |||
| Thrombocytopenia | 3/8 (37.5%) | 2/24 (8.3%) | 1/23 (4.3%) | |||
| Eye disorders | ||||||
| Dry eye | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Eye swelling | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/8 (12.5%) | 1/24 (4.2%) | 1/23 (4.3%) | |||
| Autoimmune colitis | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Constipation | 2/8 (25%) | 2/24 (8.3%) | 1/23 (4.3%) | |||
| Diarrhoea | 4/8 (50%) | 4/24 (16.7%) | 1/23 (4.3%) | |||
| Flatulence | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Nausea | 2/8 (25%) | 2/24 (8.3%) | 4/23 (17.4%) | |||
| Stomatitis | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| General disorders | ||||||
| Chills | 1/8 (12.5%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Face oedema | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Fatigue | 1/8 (12.5%) | 3/24 (12.5%) | 2/23 (8.7%) | |||
| Influenza like illness | 2/8 (25%) | 0/24 (0%) | 0/23 (0%) | |||
| Oedema peripheral | 1/8 (12.5%) | 3/24 (12.5%) | 1/23 (4.3%) | |||
| Pyrexia | 1/8 (12.5%) | 1/24 (4.2%) | 4/23 (17.4%) | |||
| Infections and infestations | ||||||
| Acute sinusitis | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Clostridium difficile colitis | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Lower respiratory tract infection | 0/8 (0%) | 0/24 (0%) | 2/23 (8.7%) | |||
| Pneumonia | 0/8 (0%) | 2/24 (8.3%) | 1/23 (4.3%) | |||
| Upper respiratory tract infection | 1/8 (12.5%) | 2/24 (8.3%) | 2/23 (8.7%) | |||
| Urinary tract infection | 1/8 (12.5%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Infusion related reaction | 2/8 (25%) | 3/24 (12.5%) | 14/23 (60.9%) | |||
| Muscle strain | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 7/8 (87.5%) | 5/24 (20.8%) | 1/23 (4.3%) | |||
| Aspartate aminotransferase increased | 7/8 (87.5%) | 5/24 (20.8%) | 1/23 (4.3%) | |||
| Blood creatinine increased | 0/8 (0%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Heart rate increased | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus | 1/8 (12.5%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Hyperglycaemia | 1/8 (12.5%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Hyperuricaemia | 0/8 (0%) | 3/24 (12.5%) | 0/23 (0%) | |||
| Hypocalcaemia | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Hypokalaemia | 1/8 (12.5%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Hyponatraemia | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Tetany | 0/8 (0%) | 0/24 (0%) | 2/23 (8.7%) | |||
| Tumour lysis syndrome | 0/8 (0%) | 0/24 (0%) | 2/23 (8.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/8 (12.5%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Back pain | 0/8 (0%) | 2/24 (8.3%) | 1/23 (4.3%) | |||
| Neck pain | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Nervous system disorders | ||||||
| Cerebellar syndrome | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Circadian rhythm sleep disorder | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Dementia | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Dizziness | 1/8 (12.5%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Dizziness postural | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Headache | 1/8 (12.5%) | 2/24 (8.3%) | 2/23 (8.7%) | |||
| Psychomotor skills impaired | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Somnolence | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Tremor | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 1/8 (12.5%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Insomnia | 2/8 (25%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Restlessness | 2/8 (25%) | 0/24 (0%) | 0/23 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal failure | 0/8 (0%) | 0/24 (0%) | 2/23 (8.7%) | |||
| Urinary retention | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Penile pain | 0/8 (0%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/8 (0%) | 2/24 (8.3%) | 0/23 (0%) | |||
| Dyspnoea | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Hypoxia | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Ecchymosis | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Night sweats | 2/8 (25%) | 0/24 (0%) | 0/23 (0%) | |||
| Rash | 1/8 (12.5%) | 1/24 (4.2%) | 0/23 (0%) | |||
| Rash macular | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
| Vascular disorders | ||||||
| Flushing | 1/8 (12.5%) | 0/24 (0%) | 1/23 (4.3%) | |||
| Hypertension | 0/8 (0%) | 2/24 (8.3%) | 1/23 (4.3%) | |||
| Orthostatic hypotension | 1/8 (12.5%) | 0/24 (0%) | 0/23 (0%) | |||
Limitations/Caveats
The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant.
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
Results Point of Contact
| Name/Title | Clinical Trial Disclosures |
|---|---|
| Organization | Gilead Sciences |
| Phone | |
| ClinicalTrialDisclosures@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01980875
Other Study ID Numbers:
- GS-US-312-0118
- 2013-004551-20
First Posted:
Nov 11, 2013
Last Update Posted:
Nov 19, 2018
Last Verified:
May 1, 2017