Efficacy and Safety of Idelalisib in Combination With Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia

A Phase 3, Randomized, Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia

The primary objective of this study is to evaluate the effect of the addition of idelalisib to ofatumumab on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL).

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Idelalisib; Drug: Ofatumumab

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Woodville, Australia, 5011
    • Queen Elizabeth Hospital
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Saint George and Sutherland Hospitals
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Milton, Queensland, Australia, 4064
      • Haematology and Oncology Clinics of Australia at Mater
  • South Australia
    • Ashford, South Australia, Australia, 5035
      • Ashford Cancer Centre Research
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Melbourne, Victoria, Australia, 3199
      • Frankston Hospital
• Belgium
  • Antwerpen, Belgium, 2060
    • Ziekenhuis Netwerk Antwerpen
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuis Gasthuisberg
• Canada
  • Winnipeg, Canada, R3E 0V9
    • Cancer Care Manitoba
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Ontario
    • Sudbury, Ontario, Canada, P3E 5J1
      • Hopital Regional De Sudbury Regional Hospital (HRSRH) - Regional Cancer Program (RCP)
  • Quebec
    • Montréal, Quebec, Canada, H1T 2M4
      • Centre Hospitalier Universitaire de Montréal
    • Rimouski, Quebec, Canada, G5L 5T1
      • Centre Hospitalier Regional De Rimouski
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 1A5
      • Saskatchewan Cancer Agency
• Denmark
  • Aalborg, Denmark, 9100
    • Aalborg Hospital
  • Århus, Denmark, 8000
    • Aarhus University Hospital
• France
  • Auvergne, France, 63000
    • CHRU Clermont- Ferrand CHU Estaing
  • Ile-de-france, France, 93009
    • Centre Hospitalier Universitaire Hopital Avicenne
  • Aquitaine
    • Pessac Cedex, Aquitaine, France, 33604
      • Center Hospitalier Universitaire de Bordeaux
  • Ile-de-france
    • Paris Cedex 10, Ile-de-france, France, 75010
      • Hôpital Saint Louis
  • Languedoc-Roussillon
    • Perpignan, Languedoc-Roussillon, France, 66046
      • Centre Hospitalier de Perpignan
  • Limousin, Lorraine
    • Vandoeuvre, Limousin, Lorraine, France, 54511
      • Centre Hospitalier Universitaire Nancy
  • Midi-pyrenees
    • Toulouse Cedex, Midi-pyrenees, France, 31059
      • Centre Hospitalier Universitaire Purpan
• Ireland
  • Cork, Ireland
    • University College Cork
  • Dublin, Ireland, 8
    • Saint James's Hospital
• Poland
  • Brzozow, Poland, 36-200
    • Szpital Specjalistyczny w Brzozowie
  • Lódz, Poland, 93-510
    • Wojewódzki Szpital Specjalistyczny im. Mikolaja Kopernika w Lodzi
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny MSW
  • Wroclaw, Poland, 50-367
    • Samodzielny Publiczny Szpital Kliniczny N1 Klinika
  • Malopolskie
    • Kraków, Malopolskie, Poland, 31-501
      • Collegium Medicum Uniwersytetu Jagiellonskiego w K
  • Pomorskie
    • Slupsk, Pomorskie, Poland, 76-200
      • Wojewódzki Szpital Specjalistyczny im. Janusza Kor
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d´hebron
  • Barcelona, Spain, 08025
    • Hospital Clinic I Provincial
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28222
    • Hospital Puerta de Hierro Majadahonda
  • Murcia, Spain, 30008
    • Hospital Morales Meseguer
• Sweden
  • Luleå, Sweden, 971 80
    • Sunderby Sjukhus
  • Stockholm, Sweden, 171 64
    • Karolinska University Hospital Solna
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital Huddinge
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Saint James's University Hospital
  • London, United Kingdom, WC1E 6BT
    • University College London
  • London, United Kingdom, NW1 2PG
    • University College London
  • Oxford, United Kingdom, OX3 7LE
    • Department of Haematology, Cancer and Haematology Centre, Churchill Hospital (Oxford University Hospitals)
  • England
    • Birmingham, England, United Kingdom, B9 5ST
      • Birmingham Heartlands Hospital
    • Dartford, England, United Kingdom, DA2 8DA
      • Darent Valley Hospital
    • Guildford, England, United Kingdom, GU2 7XX
      • Royal Surrey County Hospital NHS Trust
    • Manchester, England, United Kingdom, M20 4BX
      • Haematology and Transplant Unit
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research and Excellence (cCare)
    • San Diego, California, United States, 92120
      • Kaiser Permanente
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrative Cancer Care
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Vallejo Medical Center
  • Colorado
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente of Colorado
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Regional Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists of North Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Kentucky
    • Mount Sterling, Kentucky, United States, 40353
      • Montgomery Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders, PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1010
      • Washington University Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
    • Columbus, Ohio, United States, 43202
      • The Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Upstate Oncology Associates
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203-1781
      • Tenessee Oncology, PLLC
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

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:

• Adults with previously treated recurrent CLL who have measurable lymphadenopathy
• Require therapy for CLL
• Have experienced CLL progression < 24 months since the completion of the last prior therapy
• Have disease that is not refractory to ofatumumab

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idelalisib+ofatumumab; Randomized Initial Therapy (24 weeks): Idelalisib + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation. Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.	Drug: Idelalisib; 150 mg tablets administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101; Drug: Ofatumumab; Administered intravenously; Other Names: Arzerra®
Active Comparator: Ofatumumab; Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation. Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.	Drug: Ofatumumab; Administered intravenously; Other Names: Arzerra®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Progression-free survival (PFS) was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was CLL progression based on standard criteria (other than lymphocytosis alone) as defined by the 2008 update of the International Workshop on CLL guidelines, ie, appearance of any new lesion; increase by ≥ 50% in the sum of the products of the perpendicular diameters of measured lymph nodes (SPD); new or ≥ 50% enlargement of liver or spleen; transformation to a more aggressive histology (eg, Richter's or prolymphocytic transformation); reduction in the number of blood cells (cytopenia) attributable to CLL. PFS was analyzed using Kaplan-Meier (KM) estimates.	Randomization to End of Study (up to 60 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate was defined as the percentage of participants who achieved a best overall response of complete response or partial response.; Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy.; Partial response was defined as >1 of the following criteria: a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver size, spleen size; plus ≥ 1 of the following: ≥ 1500/μL absolute neutrophil count, > 100000/μL platelets, > 11.0 g/dL hemoglobin or 50% improvement for either of these parameters without transfusions or growth factors. Overall response rate was analyzed using KM estimates.	Randomization to End of Study (up to 60 months)
Lymph Node Response Rate	Lymph node response rate was defined as the proportion of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes.	Randomization to End of Study (up to 60 months)
Overall Survival	Overall survival was defined as the interval from randomization to death from any cause. Overall survival was analyzed using KM estimates.	Randomization to Last Long-Term Follow-Up Visit (up to maximum of 5 years)
Progression-Free Survival in Subgroup of Participants With Chromosome 17p Deletion and/or TP53 Mutation	Progression-free survival in subgroup of participants with chromosome 17p deletion and/or TP53 mutation was analyzed using KM estimates.	Randomization to End of Study (up to 60 months)
Complete Response Rate	Complete response rate was defined as the percentage of participants who achieve a complete response and maintain their response for at least 8 weeks (with a 1-week window).	Randomization to End of Study (up to 60 months)

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Gordon MJ, Huang J, Chan RJ, Bhargava P, Danilov AV. Medical comorbidities in patients with chronic lymphocytic leukaemia treated with idelalisib: analysis of two large randomised clinical trials. Br J Haematol. 2021 Feb;192(4):720-728. doi: 10.1111/bjh.16879. Epub 2020 Jun 29.
• Jones JA, Robak T, Brown JR, Awan FT, Badoux X, Coutre S, Loscertales J, Taylor K, Vandenberghe E, Wach M, Wagner-Johnston N, Ysebaert L, Dreiling L, Dubowy R, Xing G, Flinn IW, Owen C. Efficacy and safety of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukaemia: an open-label, randomised phase 3 trial. Lancet Haematol. 2017 Mar;4(3):e114-e126. doi: 10.1016/S2352-3026(17)30019-4.
• Jones J, Robak T, Wach M, Brown JR, Menter AR, Vandenberghe E, et al. Updated results of a phase 3 randomized, controlled study of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukemia (CLL) [Poster 7515]. American Society of Clinical Oncology (ASCO) 52nd Annual Meeting; 2016 02 - 06 June; Chicago, IL.
• Jones JA, Wach M, Robak T, Brown JR, Menter AR, Vanderberghe E, et al. Results of a Phase 3 Randomized, Controlled Study Evaluating the Efficacy and Safety of Idelalisib (IDELA) in Combination with Ofatumumab (OFA) for Previously Treated Chronic Lymphocytic Leukemia (CLL) [Poster 7023]. American Society of Clinical Oncology (ASCO) 51st Annual Meeting; 2015 29 May - 02 June; Chicago, IL.
• Robak T, Jones J, Wach M, Brown JR, Menter AR, Vandenberghe E, et al. Updated results of a phase 3 randomized, controlled study of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukemia (CLL) [Poster 213]. 21st Congress of the European Hematology Association (EHA); 2015 09-12 June; Copenhagen, Denmark.
• Robak T, Wach M, Jones J, Owen C, Brown J, Menter A, et al. Results Of A Phase 3 Randomized Controlled Study Evaluating The Efficacy And Safety Of Idelalisib (Idela) In Combination With Ofatumumab (Ofa) For Previously Treated Chronic Lymphocytic Leukemia (CLL) [Poster LB598]. 20th Congress of the European Hematology Association (EHA); 2015 11-14 June; Vienna, Austria.
• Flinn I, Kimby E, Cotter FE, Giles FJ, Janssens A, Pulczynski EJ, et al. A Phase 3, Randomized, Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination with Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia (CLL) [Poster TPS7131]. American Society of Clinical Oncology (ASCO); 2013 May 31-June 4; Chicago, IL.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2012
• Primary Completion (Actual): August 15, 2018
• Study Completion (Actual): August 15, 2018

Study Registration Dates

• First Submitted: August 3, 2012
• First Submitted That Met QC Criteria: August 3, 2012
• First Posted (Estimate): August 7, 2012

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Ofatumumab; CLL; Chronic Lymphocytic Leukemia; CAL-101; GS-1101
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Ofatumumab; Idelalisib
• Other Study ID Numbers: GS-US-312-0119; 2012-001236-65 (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