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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01659021
Recruitment Status : Terminated
First Posted : August 7, 2012
Results First Posted : March 31, 2017
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE August 3, 2012
First Posted Date  ICMJE August 7, 2012
Results First Submitted Date  ICMJE February 14, 2017
Results First Posted Date  ICMJE March 31, 2017
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE December 4, 2012
Actual Primary Completion Date August 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
Progression-Free Survival [ Time Frame: Randomization 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 3, 2012)
Progression-Free Survival [ Time Frame: 18 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Overall Response Rate [ Time Frame: Randomization 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.
  • Lymph Node Response Rate [ Time Frame: Randomization 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.
  • Overall Survival [ Time Frame: Randomization 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 Mutation [ Time Frame: Randomization 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.
  • Complete Response Rate [ Time Frame: Randomization 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2012)
  • Overall Response Rate [ Time Frame: 18 months ]
  • Patient Well-Being (health-related quality of life questionnaire) [ Time Frame: 18 months ]
  • Disease-Related Biomarkers [ Time Frame: 18 months ]
  • Pharmacokinetics [ Time Frame: 6 months ]
    Evaluation of plasma concentrations at peak (Cmax) and trough (Cmin)
  • Incidence of Adverse Events [ Time Frame: 18 months ]
  • Health Resource Utilization (utility measure questionnaire) [ Time Frame: 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Idelalisib in Combination With Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • Drug: Idelalisib
    150 mg tablets administered orally twice daily
    Other Names:
    • Zydelig®
    • GS-1101
    • CAL-101
  • Drug: Ofatumumab
    Administered intravenously
    Other Name: Arzerra®
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Idelalisib
    • Drug: Ofatumumab
  • 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.

    Intervention: Drug: Ofatumumab
Publications *
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 22, 2015)
261
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2012)
210
Actual Study Completion Date  ICMJE August 15, 2018
Actual Primary Completion Date August 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Denmark,   France,   Ireland,   Poland,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01659021
Other Study ID Numbers  ICMJE GS-US-312-0119
2012-001236-65 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP