Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT01980875
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 57
-
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Randomized: Obinutuzumab+chlorambucil Chlorambucil Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks. Randomized: Idelalisib+obinutuzumab Idelalisib Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Safety Run-In: Idelalisib+obinutuzumab Idelalisib 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. Safety Run-In: Idelalisib+obinutuzumab 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. Randomized: Obinutuzumab+chlorambucil Obinutuzumab Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks. Randomized: Idelalisib+obinutuzumab Obinutuzumab Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
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.
Trial Locations
- Locations (18)
Sansum Clinic
🇺🇸Santa Barbara, California, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Centre Hospitalier de Perpignan
🇫🇷Perpignan Cedex 9, France
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
UCLA Jonsson Comprehensive Cancer Center
🇺🇸Santa Monica, California, United States
Cancer Center of Central Connecticut
🇺🇸Southington, Connecticut, United States
UZ Ghent- hematology
🇧🇪Ghent, Belgium
Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
Royal Victoria Regional Health Centre - Simcoe Musk
🇨🇦Barrie, Ontario, Canada
Centre Hospitalier du Mans
🇫🇷Le Mans, France
Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej
🇵🇱Brzozow, Podkarpackie, Poland
Malopolskie Centrum Medyczne s.c.
🇵🇱Krakow, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii
🇵🇱Olsztyn, Poland
Wojewódzki Szpital Specjalistyczny w Legnicy
🇵🇱Legnica, Poland
Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego
🇵🇱Lodz, Poland
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
East Kent Hospitals University NHS Foundation Trust
🇬🇧Canterbury, Kent, United Kingdom
St Vincent Hospital, Sydney
🇦🇺Darlinghurst, New South Wales, Australia