Back to resultsEfficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Idelalisib
Chlorambucil
Obinutuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia
Eligibility Criteria
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.
Sites / Locations
- Sansum Clinic
- UCLA Jonsson Comprehensive Cancer Center
- Innovative Clinical Research Institute
- Cancer Center of Central Connecticut
- Gabrail Cancer Center Research
- Saint Francis Cancer Center
- St Vincent Hospital, Sydney
- UZ Ghent- hematology
- Royal Victoria Regional Health Centre - Simcoe Musk
- Centre Hospitalier du Mans
- Centre Hospitalier de Perpignan
- Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej
- Malopolskie Centrum Medyczne s.c.
- Wojewódzki Szpital Specjalistyczny w Legnicy
- Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii
- Hospital Universitario de Salamanca
- East Kent Hospitals University NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Safety Run-In: Idelalisib+obinutuzumab
Randomized: Idelalisib+obinutuzumab
Randomized: Obinutuzumab+chlorambucil
Arm Description
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.
Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.
Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Overall Response Rate
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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01980875
Brief Title
Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Terminated
Study Start Date
April 21, 2015 (Actual)
Primary Completion Date
May 13, 2016 (Actual)
Study Completion Date
May 13, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Safety Run-In Phase: Single Group; Randomized Phase: Parallel
Masking
None (Open Label)
Allocation
Randomized
Enrollment
57 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Safety Run-In: Idelalisib+obinutuzumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Randomized: Idelalisib+obinutuzumab
Arm Type
Experimental
Arm Description
Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.
Arm Title
Randomized: Obinutuzumab+chlorambucil
Arm Type
Active Comparator
Arm Description
Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
GS-1101, CAL-101, Zydelig®
Intervention Description
150 mg tablet administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
Chlorambucil
Intervention Description
2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Sansum Clinic
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Facility Name
UCLA Jonsson Comprehensive Cancer Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Innovative Clinical Research Institute
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Cancer Center of Central Connecticut
City
Southington
State/Province
Connecticut
ZIP/Postal Code
06489
Country
United States
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Saint Francis Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29607
Country
United States
Facility Name
St Vincent Hospital, Sydney
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
UZ Ghent- hematology
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Royal Victoria Regional Health Centre - Simcoe Musk
City
Barrie
State/Province
Ontario
ZIP/Postal Code
L4M 6M2
Country
Canada
Facility Name
Centre Hospitalier du Mans
City
Le Mans
ZIP/Postal Code
72037
Country
France
Facility Name
Centre Hospitalier de Perpignan
City
Perpignan Cedex 9
ZIP/Postal Code
66046-BP 49954
Country
France
Facility Name
Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej
City
Brzozow
State/Province
Podkarpackie
ZIP/Postal Code
36-200
Country
Poland
Facility Name
Malopolskie Centrum Medyczne s.c.
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Wojewódzki Szpital Specjalistyczny w Legnicy
City
Legnica
ZIP/Postal Code
59-220
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego
City
Lodz
ZIP/Postal Code
93-510
Country
Poland
Facility Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii
City
Olsztyn
ZIP/Postal Code
10-228
Country
Poland
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
East Kent Hospitals University NHS Foundation Trust
City
Canterbury
State/Province
Kent
ZIP/Postal Code
CT1 3NG
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency
Learn more about this trial
Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
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