Efficacy and Safety of Idelalisib in Combination With Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia With 17p Deletion

October 19, 2018 updated by: Gilead Sciences

A Phase 2, Single Arm Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia With 17p Deletion

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

102

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Liverpool, Australia, NSW 2170
        • Liverpool Hospital
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • St Vincent's Hospital, Sydney
      • Kogarah, New South Wales, Australia, 2217
        • St George Hospital
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Icon Cancer Foundation
    • Victoria
      • Fitzroy, Victoria, Australia, 3065
        • St Vincent's Hospital, Melbourne
  • Austria
      • Innsbruck, Austria, A-6020
        • Innsbruck University Hospital, Inner Medicine,
      • Salzburg, Austria, 5020
        • Univ. Klinik für Innere Medizin III LKH
      • Vienna, Austria, 1090
        • Medizinische Universität Wien, Univ. Klinik f. Innere Med. I, Abteilung für Hämatologie und Hämostaseologie
  • Belgium
      • Brugge, Belgium, 8000
        • AZ Sint-Jan AV Brugge-Oostende
      • Leuven, Belgium, 3000
        • University Hospital Leuven
  • Czechia
      • Brno, Czechia
        • University Hospital
      • Hradec Kralove, Czechia, 500 05
        • Faculty Hospital Hradec Kralove
      • Olomuc, Czechia
        • Hemato-Onkologicka Klinika Fn
      • Ostrava-Poruba, Czechia, 70852
        • Faculty Hospital Ostrava
      • Prague 10, Czechia, 10034
        • Faculty Hospital Kralovske Vinohrady
      • Praha, Czechia, 12808
        • Vseobecna Fakultim Nemocnice
  • Denmark
      • Aalborg, Denmark, 9100
        • Aalborg University Hospital
  • France
      • Bobigny, France, 93009
        • Centre Hospitalier Universitaire Hopital Avicenne
      • Lille, France, 59037
        • CHRU de Lille, Hopital Claude Huriez
      • Nancy, France, 54511
        • Centre Hospitalier Universitaire Nancy
      • Paris cedex 13, France, 75651
        • Hôpital Pitié-Salpêtrière
  • Hungary
      • Debrecen, Hungary, 4032
        • University of Debrecen HSC Institute of internal Medicine, Department of Hematology
  • Italy
      • Bologna, Italy, 40138
        • Institute of Hematology "L. e A. Seràgnoli"
      • Brescia, Italy, 25123
        • A.O.Spedali Civili Brescia
      • Milan, Italy, 20162
        • A.O.Niguarda Ca' Granda
      • Modena, Italy, 41124
        • Azienda Ospedaliero Universitaria Policlinico di Modena
      • Orbassano, Italy, 10043
        • SCDU Medicina II ed Ematologia, A.O.U. San Luigi Gonzaga
  • Poland
      • Brzozow, Poland, 36-200
        • Szpital Specjalistyczny w Brzozowie
      • Krakow, Poland, 30-510
        • Malopolskie Centrum Medyczne s.c.
      • Lodz, Poland, 93-510
        • Wojewodzki Szpital Specjalistyczny
      • Warszawa, Poland, 02-781
        • Centrum Onkologii-Instytut Marii Sklodowskiej -Curie klinika Nowotworow Ukladu Chlonnego
      • Wroclaw, Poland, 50-367
        • Samodzielny Publiczny Szpital Kliniczny
    • Pomorskie
      • Gdańsk, Pomorskie, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne
  • Portugal
      • Lisbon, Portugal, 1649-035
        • Centro Hospitalar De Lisboa Norte, E.P.E. - Hospital Santa Maria
      • Porto, Portugal, 4200-072
        • IPO Porto Francisco Gentil, E.P.E
  • Romania
      • Brasov, Romania, 500326
        • Emergency County Clinical Hospital Brasov
      • Bucharest, Romania, 20125
        • Spitalul Clinic Colentina
      • Iasi, Romania, 700348
        • Institutul Regional de Oncologie Iasi
  • Spain
      • Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia (CHUV)
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
    • Cataluña
      • Barcelona, Cataluña, Spain, 08036
        • Hospital Clínic
  • United Kingdom
      • Leeds, United Kingdom, LS9 7TF
        • Saint James's University Hospital
      • Liverpool, United Kingdom, L7 8XP
        • Royal Liverpool & Broadgreen Univ. Hospitals
      • Southampton, United Kingdom, 16
        • University Hospital Southampton NHS Trust
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85710
        • Arizona Oncology Associates, PC - HOPE
    • California
      • Whittier, California, United States, 90603
        • Innovative Clinical Research Institute
    • Colorado
      • Boulder, Colorado, United States, 80303
        • Rocky Mountain Cancer Centers
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medicine
      • Niles, Illinois, United States, 60714
        • Illinois Cancer Specialists
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University
      • Greenville, North Carolina, United States, 29615
        • GHS Cancer Institute
    • Oregon
      • Portland, Oregon, United States, 97213
        • Compass Oncology
      • Springfield, Oregon, United States, 97477
        • Willamette Valley Cancer Center and Research Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania, Abramson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • 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 Exclusion Criteria:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Idelalisib + rituximab
Participants will receive rituximab for 8 weeks and Idelalisib continuously throughout the study (up to 10 years).
Drug: Idelalisib
150 mg tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
Drug: Rituximab
375 mg/m^2 administered intravenously once weekly x 8 weeks
Other Names:
  • Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
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

Outcome Measure
Measure Description
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.
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.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 6, 2014

Primary Completion (Actual)

April 27, 2016

Study Completion (Actual)

May 17, 2016

Study Registration Dates

First Submitted

January 22, 2014

First Submitted That Met QC Criteria

January 22, 2014

First Posted (Estimate)

January 24, 2014

Study Record Updates

Last Update Posted (Actual)

November 19, 2018

Last Update Submitted That Met QC Criteria

October 19, 2018

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-312-0133
  • 2013-003314-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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 Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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