A Randomized, Double-Blind, Placebo-Controlled Study of Idelalisib in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL)

• ClinicalTrials.gov Identifier: NCT01539512
• Recruitment Status: Completed
• First Posted: February 27, 2012
• Results First Posted: October 16, 2014
• Last Update Posted: May 14, 2019
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: February 12, 2012
• First Posted Date: February 27, 2012
• Results First Submitted Date: October 9, 2014
• Results First Posted Date: October 16, 2014
• Last Update Posted Date: May 14, 2019
• Study Start Date: April 2012
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 20, 2015)

Progression-Free Survival [ Time Frame: Up to 17 months ]

Progression-free survival 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.

• Original Primary Outcome Measures (submitted: February 24, 2012): Progression Free Survival [ Time Frame: 18 Months ]

Current Secondary Outcome Measures (submitted: April 20, 2015)

• Overall Response Rate [ Time Frame: Up to 17 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.
• Lymph Node Response Rate [ Time Frame: Up to 17 months ]
  Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the SPD of index lymph nodes.
• Overall Survival [ Time Frame: Up to 17 months ]
  Overall survival was defined as the interval from randomization to death from any cause.
• Complete Response Rate [ Time Frame: Up to 17 months ]
  Complete response rate was defined as the percentage of participants who achieved a complete response.

Original Secondary Outcome Measures (submitted: February 24, 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 ]
  Pharmacokinetic to measure peak plasma concentrations (Cmax) as well as the area under the plasma concentration versus time curve (AUC).
• Incidence of Adverse Events [ Time Frame: 18 months ]
• Health Resource Utilization [ Time Frame: 18 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Randomized, Double-Blind, Placebo-Controlled Study of Idelalisib in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL)
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia
• Brief Summary: This Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the effect of idelalisib in combination with rituximab on the onset, magnitude, and duration of tumor control in participants previously treated for chronic lymphocytic leukemia (CLL). Eligible patients will be randomized with a 1:1 ratio into 1 of the 2 treatment arms to receive either idelalisib plus rituximab or placebo plus rituximab. Participants who are tolerating primary study therapy but experience definitive CLL progression are eligible to receive active idelalisib therapy in the extension study, GS-US-312-0117.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Chronic Lymphocytic Leukemia

Intervention

• Drug: Idelalisib
  Idelalisib 150 mg tablet administered orally twice daily
  Other Names:

  • Zydelig®
  • GS-1101
  • CAL 101
• Drug: Rituximab
  Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter
  Other Name: Rituxan®
• Drug: Placebo to match idelalisib
  Placebo to match idelalisib administered orally twice daily

Study Arms

• Active Comparator: Idelalisib + rituximab
  Participants will receive idelalisib plus rituximab
  Interventions:

  • Drug: Idelalisib
  • Drug: Rituximab
• Placebo Comparator: Placebo + rituximab
  Participants will receive placebo to match idelalisib plus rituximab
  Interventions:

  • Drug: Rituximab
  • Drug: Placebo to match idelalisib

Publications *

• Barrientos JC, Hillmen P, Salles G, Sharman J, Stilgenbauer S, Gurtovaya O, Xing G, Ruzicka B, Bhargava P, Ghia P, Pagel JM. No increased bleeding events in patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma treated with idelalisib. Leuk Lymphoma. 2021 Apr;62(4):837-845. doi: 10.1080/10428194.2020.1845339. Epub 2020 Dec 10.
• 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.
• Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O'Brien SM. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014 Mar 13;370(11):997-1007. doi: 10.1056/NEJMoa1315226. Epub 2014 Jan 22.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 14, 2014): 220
• Original Estimated Enrollment (submitted: February 24, 2012): 160
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion:

• Adult subjects 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
• Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Italy, United Kingdom, United States

Administrative Information

• NCT Number: NCT01539512
• Other Study ID Numbers: GS-US-312-0116; 2011-005180-24 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• 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

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Thomas Jahn, MD; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: April 2015