Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela ) (Tugela)

• ClinicalTrials.gov Identifier: NCT01569295
• Recruitment Status: Completed
• First Posted: April 3, 2012
• Results First Posted: February 27, 2018
• Last Update Posted: March 10, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: March 27, 2012
• First Posted Date: April 3, 2012
• Results First Submitted Date: December 18, 2017
• Results First Posted Date: February 27, 2018
• Last Update Posted Date: March 10, 2020
• Actual Study Start Date: June 15, 2012
• Actual Primary Completion Date: June 10, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 2, 2020)

Progression-Free Survival (PFS) [ Time Frame: Up to 84 months ]

PFS was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. PFS (months) = (minimum (date of disease progression, date of death) - date of randomization + 1)/30.4375.

• Original Primary Outcome Measures (submitted: March 30, 2012): Progression-Free Survival [ Time Frame: 18 Months ]

Current Secondary Outcome Measures (submitted: March 2, 2020)

• Overall Response Rate (ORR) [ Time Frame: Up to 84 months ]
  ORR was the percentage of participants who achieved a complete response (CR), CR with incomplete marrow recovery (CRi,) or partial response (PR) and maintained the response for at least 12 weeks. CR was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. PR 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. CRi was defined as all criteria for CR met but with persistent anemia, thrombocytopenia, neutropenia or a hypocellular bone marrow.
• Lymph Node Response Rate [ Time Frame: Up to 84 months ]
  Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lesions.
• Overall Survival [ Time Frame: Up to 84 months ]
  Overall survival (OS) was defined as the interval from randomization to death from any cause. Overall survival (months) = (date of death - date of randomization + 1)/30.4375.
• Complete Response Rate [ Time Frame: Up to 84 months ]
  Complete response (CR) rate was defined as the percentage of participants who achieved a CR.

Original Secondary Outcome Measures (submitted: March 30, 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 ]
  Peak Plasma Concentration (Cmax) and Trough Plasma Concentration (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: Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela )
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia
• Brief Summary: The primary objective of this study is to evaluate the effect of the addition of idelalisib (formerly GS-1101) to bendamustine + rituximab (BR) on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL)
• 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 administered orally twice daily
  Other Names:

  • GS-1101
  • CAL-101
  • Zydelig®
• Drug: Rituximab
  Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions
  Other Names:

  • Rituxan®
  • MabThera
• Drug: Bendamustine
  Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions
  Other Names:

  • Ribomustin
  • Treanda®
• Drug: Placebo to match idelalisib
  Placebo to match idelalisib administered orally twice daily

Study Arms

• Experimental: Idelalisib+bendamustine+rituximab
  Participants will receive idelalisib plus bendamustine and rituximab
  Interventions:

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

  • Drug: Rituximab
  • Drug: Bendamustine
  • Drug: Placebo to match idelalisib

Publications *

• Zelenetz AD, Robak T, et al. Idelalisib Plus Bendamustine and Rituximab (BR) Is Superior to BR Alone in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results of a Phase 3 Randomized Double-Blind Placebo-Controlled Study. American Society ofHematology (ASH) 57th Annual Meeting & Exposition; 5-8 December 2015; Orlando, FL.
• Barrientos JC, Brown JR, et al. Results of a Randomized Double-Blind Placebo-Controlled Phase 3 study Evaluating Idelalisib in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL and Adverse Prognostic Features. American Society of Clinical Oncology (ASCO) 2016 Annual Meeting; 3-7 June 2016; Chicago, IL.
• Hillmen, P, Ferra C, et al. Idelalisib in Combination with Bendamustine and Rituximab Improves Overall Survival in Patients with Relapsed/Refractory CLL: Interim Results of a Phase 3 Randomized Double-Blind Placebo-Controlled Study. European Hematology Association (EHA) 21st Annual Meeting; 9-12 June 2016; Copenhagen, Denmark.
• Zelenetz AD, Brown JR et al. Updated Analysis of Overall Survival in Randomized Phase III Study of Idelalisib in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL. American Society of Hematology (ASH) 58th Annual Meeting & Exposition; 3-6 December 2016; San Diego, CA
• Zelenetz AD, Barrientos JC, Brown JR, Coiffier B, Delgado J, Egyed M, Ghia P, Illes A, Jurczak W, Marlton P, Montillo M, Morschhauser F, Pristupa AS, Robak T, Sharman JP, Simpson D, Smolej L, Tausch E, Adewoye AH, Dreiling LK, Kim Y, Stilgenbauer S, Hillmen P. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017 Mar;18(3):297-311. doi: 10.1016/S1470-2045(16)30671-4. Epub 2017 Jan 28.
• Montillo M, Illes A, Robak T, Pristupa AS, Wach M, Egyed M, Delgado J, Jurczak W, Morschhauser F, Schuh A, Eradat H, Shreay S, Barrientos JC, Zelenetz AD. Idelalisib addition has neutral to beneficial effects on quality of life in bendamustine/rituximab-treated patients: results of a phase 3, randomized, controlled trial. Health Qual Life Outcomes. 2019 Nov 15;17(1):173. doi: 10.1186/s12955-019-1232-8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 24, 2016): 416
• Original Estimated Enrollment (submitted: March 30, 2012): 390
• Actual Study Completion Date: June 10, 2019
• Actual Primary Completion Date: June 10, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Previously treated recurrent CLL
• Measurable lymphadenopathy
• Requires therapy for CLL
• Has experienced CLL progression < 36 months since the completion of the last prior therapy

Key Exclusion Criteria:

• Recent history of a major non-CLL malignancy
• Evidence of an ongoing infection
• CLL refractory to bendamustine
• Concurrent participation in another therapeutic clinical trial

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

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: Australia, Belgium, Canada, Croatia, Czechia, France, Greece, Hungary, Ireland, Italy, Poland, Portugal, Romania, Russian Federation, Spain, Turkey, United Kingdom, United States
• Removed Location Countries: Argentina, Czech Republic, New Zealand

Administrative Information

• NCT Number: NCT01569295
• Other Study ID Numbers: GS-US-312-0115; 2011-006292-20 ( 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

• 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 https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• 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: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

• 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: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: March 2020