Efficacy and Safety of Idelalisib in Combination With Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia With 17p Deletion
- Conditions
- B-cell Chronic Lymphocytic Leukemia (CLL) With 17p Deletion
- Interventions
- Registration Number
- NCT02044822
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate overall response rate (ORR) following treatment with idelalisib plus rituximab in participants with previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion.
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
- 102
- Documented diagnosis of B-cell CLL, according to International Workshop on Chronic Lymphocytic Leukemia 2008
- Presence of 17p deletion in CLL cells as demonstrated by fluorescence in-situ hybridization (FISH) testing
- 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
-
History of a non-CLL malignancy except for the following:
- the malignancy has been in remission without treatment for ≥ 5 years prior to enrollment, or
- carcinoma in situ of the cervix, or
- adequately treated basal or squamous cell skin cancer or other localized non-melanoma skin cancer, or
- asymptomatic prostate cancer without known metastatic disease and with no current requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥ 1 year prior to enrollment, or
- ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone, or
- other adequately treated Stage 1 or 2 cancer currently in complete remission
-
Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
-
Ongoing liver injury
-
History of noninfectious pneumonitis
-
Ongoing inflammatory bowel disease
-
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
-
Ongoing immunosuppressive therapy other than corticosteroids
-
Received last dose of study drug on another therapeutic clinical trial within 30 days prior to enrollment
-
Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Idelalisib + rituximab Rituximab Participants will receive rituximab for 8 weeks and Idelalisib continuously throughout the study (up to 10 years). Idelalisib + rituximab Idelalisib Participants will receive rituximab for 8 weeks and Idelalisib continuously throughout the study (up to 10 years).
- Primary Outcome Measures
Name Time Method Overall Response Rate Overall response rate (ORR) was defined as the proportion of participants who achieve a confirmed complete or partial response. ORR was to be assessed by an independent review committee (IRC).
- Secondary Outcome Measures
Name Time Method Duration of Response Duration of response (DOR) was defined as the interval from the first documentation of confirmed complete response or partial response (by IRC) to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is chronic lymphocytic leukemia (CLL) progression based on standard criteria, excluding lymphocytosis alone.
Progression-Free Survival Progression-free survival (PFS) was defined as the interval from first dose of study drug 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 IRC.
Overall Survival Overall survival was defined as the interval from the start of study treatment to death from any cause.
Nodal Response Rate Nodal response rate was 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 was defined as the proportion of participants who achieve a confirmed complete response. Complete response rate was to be assessed by an IRC.
Minimal Residual Disease Negativity Rate at Week 36 Minimal residual disease (MRD) negativity rate was 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 rituximab after the original scheduled date, the MRD assessment will be performed no fewer than 12 weeks after the last dose of rituximab.
Trial Locations
- Locations (56)
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
The University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
GHS Cancer Institute
🇺🇸Greenville, North Carolina, United States
Compass Oncology
🇺🇸Portland, Oregon, United States
Hospital of the University of Pennsylvania, Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Willamette Valley Cancer Center and Research Institute
🇺🇸Springfield, Oregon, United States
St Vincent's Hospital, Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Icon Cancer Foundation
🇦🇺South Brisbane, Queensland, Australia
Liverpool Hospital
🇦🇺Liverpool, Australia
AZ Sint-Jan AV Brugge-Oostende
🇧🇪Brugge, Belgium
Hemato-Onkologicka Klinika Fn
🇨🇿Olomuc, Czechia
Faculty Hospital Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Faculty hospital Ostrava
🇨🇿Ostrava-Poruba, Czechia
Vseobecna Fakultim Nemocnice
🇨🇿Praha, Czechia
Faculty Hospital Kralovske Vinohrady
🇨🇿Prague 10, Czechia
University Hospital
🇨🇿Brno, Czechia
Centre Hospitalier Universitaire Hôpital Avicenne
🇫🇷Bobigny, France
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Centre Hospitalier Universitaire Nancy
🇫🇷Nancy, France
CHRU de Lille, Hopital Claude Huriez
🇫🇷Lille, France
Hopital Pitie-Salpetriere
🇫🇷Paris cedex 13, France
A.O.Spedali Civili Brescia
🇮🇹Brescia, Italy
A.O.Niguarda Ca' Granda
🇮🇹Milan, Italy
Institute of Hematology "L. e A. Seràgnoli"
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Policlinico di Modena
🇮🇹Modena, Italy
SCDU Medicina II ed Ematologia, A.O.U. San Luigi Gonzaga
🇮🇹Orbassano, Italy
Wojewodzki Szpital Specjalistyczny
🇵🇱Lodz, Poland
IPO Porto Francisco Gentil, E.P.E
🇵🇹Porto, Portugal
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Clinic
🇪🇸Barcelona, Cataluña, Spain
Hospital Universitario Puerta De Hierro
🇪🇸Madrid, Spain
Hospital Clinico Universitario De Valencia (Chuv)
🇪🇸Valencia, Spain
Saint James's University Hospital
🇬🇧Leeds, United Kingdom
Royal Liverpool & Broadgreen Univ. Hospitals
🇬🇧Liverpool, United Kingdom
University Hospital Southampton NHS Trust
🇬🇧Southampton, United Kingdom
Rocky Mountain Cancer Centers
🇺🇸Boulder, Colorado, United States
University of Debrecen HSC Institute of internal Medicine, Department of Hematology
🇭🇺Debrecen, Hungary
Medizinische Universität Wien, Univ. Klinik f. Innere Med. I, Abteilung für Hämatologie und Hämostaseologie
🇦🇹Vienna, Austria
Duke University
🇺🇸Durham, North Carolina, United States
Innsbruck University Hospital, Inner Medicine,
🇦🇹Innsbruck, Austria
Univ. Klinik für Innere Medizin III LKH
🇦🇹Salzburg, Austria
St Vincent's Hospital, Melbourne
🇦🇺Fitzroy, Victoria, Australia
University Hospital Leuven
🇧🇪Leuven, Belgium
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Pomorskie, Poland
Centrum Onkologii-Instytut Marii Sklodowskiej -Curie klinika Nowotworow Ukladu Chlonnego
🇵🇱Warszawa, Poland
Samodzielny Publiczny Szpital Kliniczny
🇵🇱Wroclaw, Poland
Emergency County Clinical Hospital Brasov
🇷🇴Brasov, Romania
Szpital Specjalistyczny w Brzozowie
🇵🇱Brzozow, Poland
Malopolskie Centrum Medyczne s.c.
🇵🇱Krakow, Poland
Institutul Regional de Oncologie Iasi
🇷🇴Iasi, Romania
Centro Hospitalar De Lisboa Norte, E.P.E. - Hospital Santa Maria
🇵🇹Lisbon, Portugal
Spitalul Clinic Colentina
🇷🇴Bucharest, Romania
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States