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

Phase 3
Terminated
Conditions
Chronic Lymphocytic Leukemia
Interventions
Registration Number
NCT01659021
Lead Sponsor
Gilead Sciences
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
261
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.

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Idelalisib+ofatumumabIdelalisibRandomized 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.
OfatumumabOfatumumabRandomized 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.
Idelalisib+ofatumumabOfatumumabRandomized 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.
Primary Outcome Measures
NameTimeMethod
Progression-Free SurvivalRandomization to End of Study (up to 60 months)

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.

Secondary Outcome Measures
NameTimeMethod
Lymph Node Response RateRandomization to End of Study (up to 60 months)

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.

Complete Response RateRandomization to End of Study (up to 60 months)

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).

Overall Response RateRandomization to End of Study (up to 60 months)

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.

Overall SurvivalRandomization to Last Long-Term Follow-Up Visit (up to maximum of 5 years)

Overall survival was defined as the interval from randomization to death from any cause. Overall survival was analyzed using KM estimates.

Progression-Free Survival in Subgroup of Participants With Chromosome 17p Deletion and/or TP53 MutationRandomization to End of Study (up to 60 months)

Progression-free survival in subgroup of participants with chromosome 17p deletion and/or TP53 mutation was analyzed using KM estimates.

Trial Locations

Locations (78)

Saint Mary's Regional Cancer Center

🇺🇸

Grand Junction, Colorado, United States

Northwest Medical Specialties

🇺🇸

Tacoma, Washington, United States

City of Hope

🇺🇸

Duarte, California, United States

Haematology and Oncology Clinics of Australia at Mater

🇦🇺

Milton, Queensland, Australia

Kaiser Permanente of Colorado

🇺🇸

Denver, Colorado, United States

Georgia Regents University

🇺🇸

Augusta, Georgia, United States

Weill Cornell Medical Center

🇺🇸

New York, New York, United States

Coastal Integrative Cancer Care

🇺🇸

San Luis Obispo, California, United States

Montgomery Cancer Center

🇺🇸

Mount Sterling, Kentucky, United States

Universitair Ziekenhuis Gent

🇧🇪

Ghent, Belgium

Centre Hospitalier Universitaire Hôpital Avicenne

🇫🇷

Ile-de-france, France

Hospital Clínic i Provincial

🇪🇸

Barcelona, Spain

Cancer Care Manitoba

🇨🇦

Winnipeg, Canada

Saint George and Sutherland Hospitals

🇦🇺

Kogarah, New South Wales, Australia

Prince of Wales Hospital

🇦🇺

Randwick, New South Wales, Australia

Centre Hospitalier Universitaire Nancy

🇫🇷

Vandoeuvre, Limousin, Lorraine, France

Saint James's University Hospital

🇬🇧

Leeds, United Kingdom

Center for Cancer and Blood Disorders, PC

🇺🇸

Bethesda, Maryland, United States

Washington University Medical Center

🇺🇸

Saint Louis, Missouri, United States

Karolinska University Hospital Solna

🇸🇪

Stockholm, Sweden

Center Hospitalier Universitaire de Bordeaux

🇫🇷

Pessac Cedex, Aquitaine, France

Centre Hospitalier de Perpignan

🇫🇷

Perpignan, Languedoc-Roussillon, France

CHRU Clermont- Ferrand CHU Estaing

🇫🇷

Auvergne, France

Department of Haematology, Cancer and Haematology Centre, Churchill Hospital (Oxford University Hospitals)

🇬🇧

Oxford, United Kingdom

Queen Elizabeth Hospital

🇦🇺

Woodville, Australia

Hopital Regional De Sudbury Regional Hospital (HRSRH) - Regional Cancer Program (RCP)

🇨🇦

Sudbury, Ontario, Canada

Sunderby Sjukhus

🇸🇪

Luleå, Sweden

Centre Hospitalier Universitaire Purpan

🇫🇷

Toulouse Cedex, Midi-pyrenees, France

Hospital Morales Meseguer

🇪🇸

Murcia, Spain

California Cancer Associates for Research and Excellence (CCARE)

🇺🇸

Fresno, California, United States

The Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

Tenessee Oncology, PLLC

🇺🇸

Nashville, Tennessee, United States

Kaiser Permanente Vallejo Medical Center

🇺🇸

Vallejo, California, United States

Utah Cancer Specialists

🇺🇸

Salt Lake City, Utah, United States

Saskatchewan Cancer Agency

🇨🇦

Regina, Saskatchewan, Canada

Haematology and Transplant Unit

🇬🇧

Manchester, England, United Kingdom

Kaiser Permanente

🇺🇸

San Diego, California, United States

Cancer Specialists of North Florida

🇺🇸

Jacksonville, Florida, United States

Oncology Hematology Care, Inc.

🇺🇸

Cincinnati, Ohio, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Ashford Cancer Centre Research

🇦🇺

Ashford, South Australia, Australia

Centre Hospitalier Universitaire de Montréal

🇨🇦

Montréal, Quebec, Canada

Wojewódzki Szpital Specjalistyczny im. Janusza Kor

🇵🇱

Slupsk, Pomorskie, Poland

Hospital Universitario La Princesa

🇪🇸

Madrid, Spain

Hospital Puerta de Hierro Majadahonda

🇪🇸

Madrid, Spain

Aalborg Hospital

🇩🇰

Aalborg, Denmark

Aarhus University Hospital

🇩🇰

Århus, Denmark

Hôpital Saint Louis

🇫🇷

Paris Cedex 10, Ile-de-france, France

Karolinska University Hospital Huddinge

🇸🇪

Stockholm, Sweden

Frankston Hospital

🇦🇺

Melbourne, Victoria, Australia

Collegium Medicum Uniwersytetu Jagiellonskiego w K

🇵🇱

Kraków, Malopolskie, Poland

Norfolk and Norwich University Hospital

🇬🇧

Norwich, Norfolk, United Kingdom

University College London

🇬🇧

London, United Kingdom

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Tennessee Oncology, PLLC

🇺🇸

Chattanooga, Tennessee, United States

Comprehensive Cancer Centers of Nevada

🇺🇸

Las Vegas, Nevada, United States

Upstate Oncology Associates

🇺🇸

Greenville, South Carolina, United States

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Ziekenhuis Netwerk Antwerpen

🇧🇪

Antwerpen, Belgium

Cliniques Universitaires Saint Luc

🇧🇪

Brussels, Belgium

Centralny Szpital Kliniczny MSW

🇵🇱

Warszawa, Poland

Samodzielny Publiczny Szpital Kliniczny N1 Klinika

🇵🇱

Wroclaw, Poland

Darent Valley Hospital

🇬🇧

Dartford, England, United Kingdom

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

Universitaire Ziekenhuis Gasthuisberg

🇧🇪

Leuven, Belgium

Birmingham Heartlands Hospital

🇬🇧

Birmingham, England, United Kingdom

Royal Surrey County Hospital NHS Trust

🇬🇧

Guildford, England, United Kingdom

University College Cork

🇮🇪

Cork, Ireland

Szpital Specjalistyczny w Brzozowie

🇵🇱

Brzozow, Poland

Centre Hospitalier Regional de Rimouski

🇨🇦

Rimouski, Quebec, Canada

Saint James's Hospital

🇮🇪

Dublin, Ireland

Wojewódzki Szpital Specjalistyczny im. Mikolaja Kopernika w Lodzi

🇵🇱

Lódz, Poland

Hospital Vall d´Hebrón

🇪🇸

Barcelona, Spain

Royal Brisbane and Women's Hospital

🇦🇺

Herston, Queensland, Australia

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Stanford University Medical Center

🇺🇸

Stanford, California, United States

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

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