Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
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
2 other identifiers
interventional
57
8 countries
18
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Apr 2015
Shorter than P25 for phase_3
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 5, 2013
CompletedFirst Posted
Study publicly available on registry
November 11, 2013
CompletedStudy Start
First participant enrolled
April 21, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 13, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 13, 2016
CompletedResults Posted
Study results publicly available
June 28, 2017
CompletedNovember 19, 2018
May 1, 2017
1.1 years
November 5, 2013
March 30, 2017
October 19, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival
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).
Up to 11 months
Secondary Outcomes (5)
Overall Response Rate
Up to 11 months
Nodal Response Rate
Up to 11 months
Complete Response Rate
Up to 11 months
Overall Survival
Up to 11 months
Minimal Residual Disease Negativity Rate at Week 36
Up to 11 months
Study Arms (3)
Safety Run-In: Idelalisib+obinutuzumab
EXPERIMENTALParticipants 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.
Randomized: Idelalisib+obinutuzumab
EXPERIMENTALParticipants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.
Randomized: Obinutuzumab+chlorambucil
ACTIVE COMPARATORParticipants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.
Interventions
150 mg tablet administered orally twice daily
2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (18)
Sansum Clinic
Santa Barbara, California, 93105, United States
UCLA Jonsson Comprehensive Cancer Center
Santa Monica, California, 90404, United States
Innovative Clinical Research Institute
Whittier, California, 90603, United States
Cancer Center of Central Connecticut
Southington, Connecticut, 06489, United States
Gabrail Cancer Center Research
Canton, Ohio, 44718, United States
Saint Francis Cancer Center
Greenville, South Carolina, 29607, United States
St Vincent Hospital, Sydney
Darlinghurst, New South Wales, 2010, Australia
UZ Ghent- hematology
Ghent, 9000, Belgium
Royal Victoria Regional Health Centre - Simcoe Musk
Barrie, Ontario, L4M 6M2, Canada
Centre Hospitalier du Mans
Le Mans, 72037, France
Centre Hospitalier de Perpignan
Perpignan, 66046-BP 49954, France
Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej
Brzozów, Podkarpackie Voivodeship, 36-200, Poland
Malopolskie Centrum Medyczne s.c.
Krakow, 30-510, Poland
Wojewódzki Szpital Specjalistyczny w Legnicy
Legnica, 59-220, Poland
Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego
Lodz, 93-510, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii
Olsztyn, 10-228, Poland
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
East Kent Hospitals University NHS Foundation Trust
Canterbury, Kent, CT1 3NG, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study was terminated in agreement with the FDA due to urgent safety measures. Complete data were not collected for any participant.
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 5, 2013
First Posted
November 11, 2013
Study Start
April 21, 2015
Primary Completion
May 13, 2016
Study Completion
May 13, 2016
Last Updated
November 19, 2018
Results First Posted
June 28, 2017
Record last verified: 2017-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 18 months after study completion
- Access Criteria
- A secured external environment with username, password, and RSA code.
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.