Extension Study of Idelalisib in Participants With Chronic Lymphocytic Leukemia (CLL) Who Participated in GS-US-312-0116 (NCT01539512)

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase 3, Double-Blind Extension Study Evaluating the Efficacy and Safety of Two Different Dose Levels of Single-Agent Idelalisib (GS-1101) for Previously Treated Chronic Lymphocytic Leukemia A Companion Trial to Study GS-US-312-0116: 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01539291
• Other study ID #: GS-US-312-0117
• Secondary ID: 2011-006293-72
• Status: Terminated
• Phase: Phase 3
• Start date: October 3, 2012
• Est. completion date: June 29, 2018

Study information

• Verified date: August 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this extension study (GS-US-312-0117) that is a companion study to Study GS-US-312-0116 (NCT01539512), is to evaluate the effect of idelalisib on the onset, magnitude, and duration of tumor control. Randomization was done in study GS-US-312-0116, and carried forward to study GS-US-312-117.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 161
• Est. completion date: June 29, 2018
• Est. primary completion date: May 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Individuals in the primary Phase 3 study (Study GS-US-312-0116) who are compliant

• Tolerating primary study therapy

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Idelalisib
Idelalisib tablet(s) administered orally twice daily

Locations

Country	Name	City	State
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Centre Henri Becquerel	Rouen
Germany	Hämatologische und Internistische Gemeinschaftspraxis Dres. Eckart / Häcker	Erlangen
Germany	Universitätsklinikum Köln	Köln
Italy	Ospedale San Raffaele S.r.l.	Milano
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Dorset County Hospital	Dorchester
United Kingdom	Northwick Park Hospital	Harrow
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	Hammersmith Hospital	London
United Kingdom	Princess Royal University Hospital	Orpington
United Kingdom	Southampton General Hospital	Southampton
United States	Collaborative Research Group	Boynton Beach	Florida
United States	Northwestern University	Chicago	Illinois
United States	Rocky Mountain Blood and Marrow Transplant Program	Denver	Colorado
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Texas Oncology, P.A.	Fort Worth	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	University of California, San Diego - Moores Cancer Center	La Jolla	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Cancer Care Network of South Texas	San Antonio	Texas
United States	UCLA	Santa Monica	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Willamette Valley Cancer Center	Springfield	Oregon
United States	Stanford Cancer Center	Stanford	California
United States	Northwest Cancer Specialists, PC	Tualatin	Oregon
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  United Kingdom, 

References & Publications (3)

Coutre SE, Furman RR, Sharman, JP, Cheson BD, Pagel JM, Hillmen P, et al. Second Interim Analysis of a Phase 3 Study of Idelalisib (Zydelig®) Plus Rituximab for Relapsed Chronic Lymphocytic Leukemia: Efficacy Analysis in Patient Subpopulations with Del(17

Sharman JP, Coutre SE, Furman RR, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn IW, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Tausch E, Cramer P, Huang J, Mitra S, Hallek M, O'Brien SM, Stilgenbauer — View Citation

Sharman JP, Coutre SE, Furman RR, Cheson BD, Pagel JM, Hillmen P, et al. Efficacy of Idelalisib in CLL Subpopulations Harboring Del(17p) and Other Adverse Prognostic Factors: Results from a Phase 3, Randomized, Double-blind, Placebo-controlled Trial [Post

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS was defined as the interval from the start of study therapy to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is chronic lymphocytic leukemia (CLL) progression based on standard criteria other than lymphocytosis alone. PFS was analyzed using Kaplan-Meier (KM) estimates.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Primary	Safety: Percentage of Participants With Any Treatment-Emergent Adverse Events (TEAE), = Grade 3 TEAE, Study Drug-Related TEAE, = Grade 3 Study Drug-Related TEAE, Serious TEAE, Study Drug-Related Serious TEAE, and TEAE Leading to Study Drug Discontinuation	The TEAEs were defined as events in a given study period that met one of the following criteria: Events with onset dates on or after the start of treatment and up to 30 days after the permanent discontinuation of the study treatment.; The continuing adverse events (AEs) diagnosed prior to the start of treatment and worsened in severity grade, or non-serious AEs at baseline which became serious, or AEs resulting in treatment discontinuation after the start of treatment.; The severity of AEs was graded by the investigator according to the common terminology criteria for adverse events (CTCAE), Version 4.03, whenever possible. The relationship of an AE to study drug (idelalisib) was assessed using clinical judgment by the investigator, describing the event as either unrelated or related. Events for which the investigator did not record relationship to study drug were considered related to study drug.	First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months) plus 4 weeks
Secondary	Overall Response Rate (ORR)	ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR). The determination of CLL response and progression were based on standardized International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria, as specifically modified for this study to reflect current recommendations which considered the mechanism of action of idelalisib and similar drugs. CR and PR are defined in Protocol Amendment 9, Sections 7.5.1 and 7.5.2.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Lymph Node Response Rate	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 lymph nodes.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Complete Response (CR) Rate	CR rate was defined as the percentage of participants who achieved a CR (full definition in Protocol Amendment 9, Section 7.5.1). The determination of CLL response and progression were based on standardized IWCLL criteria, as specifically modified for this study to reflect current recommendations which considered the mechanism of action of idelalisib and similar drugs.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Time to Response (TTR)	TTR was defined as the time interval from start of study therapy to the first documentation of CR or PR.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Duration of Response (DOR)	DOR was defined as the time interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. DOR was analyzed using KM estimates.	From first documentation of CR or PR to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Best Percent Change in Lymph Node Area	The best percent change from baseline in lymph node area (SPD) was defined as the largest decrease in tumor size during the study. The baseline SPD was the last value prior to the baseline reference date. For the participants who only had increases in tumor size from baseline, the smallest increase was considered as the best change from baseline in SPD.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Splenomegaly Response Rate	Splenomegaly response rate was defined as the percentage of participants with baseline splenomegaly who achieved an on-study normalization or a 50% decrease (minimum 2 cm) from baseline in the enlargement of the splenic longest vertical dimension (LVD) (by imaging).	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Hepatomegaly Response Rate	Hepatomegaly response rate was defined as the percentage of participants with baseline hepatomegaly who achieved an on-study normalization or a 50% decrease (minimum 2 cm) from baseline in the hepatic LVD (by imaging).	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Absolute Lymphocyte Count (ALC) Response Rate	ALC response rate was defined as the percentage of participants with baseline lymphocytosis (ALC = 4 x 10^9 cells/L) who achieved an on-study ALC < 4 x 10^9 cells/L or demonstrated a = 50% decrease in ALC from baseline; ALC values within 4 weeks post-baseline were excluded from the ALC response rate evaluation.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Platelet Response Rate	Platelet response rate was defined as the percentage of participants with baseline thrombocytopenia (platelet count < 100 x 10^9/L) who achieved an on-study platelet count = 100 x 10^9/L or demonstrated a = 50% increase in platelet count from baseline; platelet values within 4 weeks post-baseline or after 8 days post transfusion were excluded from the platelet response rate evaluation.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Hemoglobin Response Rate	Hemoglobin response rate was defined as the percentage of participants with baseline anemia (hemoglobin < 110 g/L [11.0 g/dL]) who achieved an on-study hemoglobin = 110 g/L (11.0 g/dL) or demonstrated a = 50% increase in hemoglobin from baseline; hemoglobin values within 4 weeks post-baseline or after 4 weeks of receiving packed cell/whole blood transfusion or after 6 weeks of receiving exogenous growth factors (eg, darbepoetin alfa) were excluded from the hemoglobin response evaluation.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Neutrophil Response Rate	Neutrophil response rate was defined as the percentage of participants with baseline neutropenia (absolute neutrophil count [ANC] = 1.5 x 10^9/L) who achieved an ANC > 1.5 x 10^9/L or demonstrated a = 50% increase in ANC from baseline; ANC values within 4 weeks of post-baseline or after 2 weeks of receiving exogenous growth factors (eg, filgrastim, granulocyte-colony stimulating factor [G-CSF], lenograstim) or after 4 weeks of receiving Neulasta® were excluded from response evaluation.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Overall Survival	Overall survival was defined as the time interval from start of study therapy to death from any cause. Overall survival was analyzed using KM estimates. Data presented includes all available survival information from Study GS-US-312-0116 (including data in long-term follow-up) and Study GS-US-312-0117 (including any data in long-term follow-up) up to the database finalization dates. Data from surviving participants were censored at the last time that the participant was known to be alive on study or long-term follow-up. Data presented includes all participants who were randomized to Study GS-US-312-0116 regardless if they entered Study GS-US-312-0117 or not.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Best Change From Baseline in Health-Related Quality of Life (HRQL) Domain and Symptom Scores Based on the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) Questionnaire	The FACT-Leu questionnaire included subscales for physical well-being (PWB, 7 items), social/family well-being (SWB, 7 items), emotional well-being (EWB, 6 items), functional well-being (FWB, 7 items), and additional concerns or Leukemia-Specific Subscale (LeuS, 17 items). The FACT-Leu scoring guide identified those negatively stated items that must have been reversed before being added to obtain subscale totals. Negatively stated items were reversed by subtracting the response from "4". After reversing proper items, all subscale items were summed to get total subscale scores with the range of 0-28, 0-28, 0-24, 0-28, 0-68 for PWB, SWB, EWB, FWB, and LeuS, respectively. FACT-Leu total score ranged from 0 to 176. Higher scores indicated a better quality of life. Best change from baseline was defined as the highest value of change from baseline among all postbaseline visits. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.	Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 184
Secondary	Best Change From Baseline in Karnofsky Performance Status (KPS)	KPS is a tool used to measure the ability to perform ordinary tasks. The score ranges from 0 to 100, with a higher score indicating that the participant is better able to carry out daily activities. Best change from baseline was defined as the highest value of change from baseline among all postbaseline visits. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.	Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 190
Secondary	Changes From Baseline in Phosphatidylinositol 3-kinase (PI3Kd)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway Activation as a Measure of PI3Kd Pathway Activity		GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines	The percent of average on-treatment biomarker concentration of baseline (%Baseline) was used to evaluate the overall pharmacodynamics change on the biomarkers with IDL treatment. The average on-treatment biomarker concentration is calculated using area under curve (AUC) following the trapezoidal rule. The biomarkers with median AUC value of 100 indicated no overall on-treatment biomarker changes compared to the baseline. The biomarkers with median AUC value greater than 100 or less than 100 indicated an increase or decrease, respectively, on-treatment biomarker changes from the baseline.	GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Secondary	Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment	Adherence percentage was calculated as the sum of tablets dispensed - the sum of tablets returned divided by the sum of the overall dosing period (total daily tablets x dosing duration), taking into account investigator-prescribed interruptions.	First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months)
Secondary	Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib		Weeks 4, 12, and 24
Secondary	Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure	Change in health status was defined as the change from baseline in overall health and single-item dimension scores as assessed using the EQ-5D utility measure. Percentage of participants with different level of problem were reported. Level 1: indicated no problem; Level 2: indicated some problems; and Level 3: indicated extreme problems. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.	Study GS-US-312-0116 or GS-US-312-0117 Baseline; Weeks 24 and 48