A Phase 3, Double-Blind Extension Study of Idelalisib (GS-1101) at Different Dose Levels for Previously Treated CLL patients (a Companion Trial to GS-US-312-0116)

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2011-006293-72-GB
• Date of registration: 12/03/2012
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A Phase 3, Double-Blind Extension Study of Idelalisib (GS-1101) at Different Dose Levels for Previously Treated CLL patients (a Companion Trial to GS-US-312-0116)
• Scientific 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
• Date of first enrolment: 08/05/2012
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006293-72
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: GS-1101 Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, United Kingdom, United States

Contacts

• Name: Clinical Trial Mailbox
• Affiliation: Gilead Sciences International Ltd

• Name: Clinical Trial Mailbox
• Affiliation: Gilead Sciences International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
1) Participation in Study GS-US-312-0116.
2) Occurrence of confirmed, definitive CLL progression while receiving study drug therapy (idelalisib/placebo) in Study GS US 312 0116. Note: Definitive disease progression is CLL progression based on standard criteria and occurring for any reason (ie, increasing lymphadenopathy, organomegaly, or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other than lymphocytosis. Subjects must have confirmation by the sponsor working in collaboration with an independent review committee (IRC) that the disease has progressed on the clinical trial (Study GS-US-312-0116) before receiving secondary GS 1101 therapy on this extension trial (Study GS-US-312-0117).
3) Presence of radiographically measurable lymphadenopathy (defined as the presence of =1 nodal lesion that measures =2.0 cm in the longest diameter [LD] and =1.0 cm in the longest perpendicular diameter [LPD] as assessed by CT or MRI).
4) Permanent cessation of Study GS-US-312-0116 treatment (rituximab and idelalisib/placebo) and no intervening or continuing therapy (including radiotherapy, chemotherapy, immunotherapy or investigational therapy) for the treatment of CLL. Note: subjects may receive corticosteroids to manage CLL manifestations.
5) The time from permanent cessation of Study GS-US-312-0116 treatment (rituximab and/or GS-1101/placebo) and the initiation of Study GS-US-312-0117 therapy is =12 weeks. Note: Study procedures performed as part of Study GS-US-312-0116 need not be repeated and can be used as screening procedures for Study GS-US-312-0117 if performed within 4 weeks prior to initiation of study drug therapy on Study GS-US-312-0117.
6) Karnofsky performance score of =40.
7) Required baseline laboratory data (within 4 weeks prior to initiation of study treatment) as shown in the table below. Note: Confirmation should be considered for out-of-range values to determine if the abnormality is real or artifactual. Values should be obtained within the screening period and should generally be the most recent measurement obtained. Subjects with any degree of neutropenia, thrombocytopenia, or anemia due to CLL or prior therapy may enroll.
8) For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the screening visit (Visit 1) throughout the study and for 30 days from the last dose of study drug. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional postmenopausal range and a negative serum or urine ßHCG), or is menopausal (defined as age =54 years with amenorrhae for>12 months or amenorrhae for > 6 months with serum estrdiol and FSH levels within the institutional postmenopausal range).
9) For male subjects of childbearing potential having intercourse with females of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of study drug (Visit 2) throu
Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1) Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation). Note: Biopsy documentation of the absence or presence of transformation is not required.
2) Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of the start of study treatment (Visit 2). Note: Subjects with localized fungal infections of skin or nails are eligible. Subjects may be receiving prophylactic antiviral or antibacterial therapies at the discretion of the investigator; anti-pneumocystis prophylaxis is encouraged. For subjects who are at substantial risk of an infection (eg,influenza) that may be prevented by immunization, consideration should be given to providing the vaccine prior to initiation of protocol therapy.
3) Pregnancy or breastfeeding.
4) Intentional breaking of the blind in Study GS-US-312-0116 by the investigator or the study subject.
5) Concurrent participation in another therapeutic clinical trial.
6) Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Chronic lymphocytic leukemia (CLL)
MedDRA version: 20.0 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Code: GS-1101
Pharmaceutical Form: Tablet
INN or Proposed INN: Idelalisib
CAS Number: 870281-82-6
Current Sponsor code: GS-1101
Other descriptive name: CAL-101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: Idelalisib
CAS Number: 870281-82-6
Current Sponsor code: GS-1101
Other descriptive name: CAL-101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: determining the effect of GS-1101 on the onset, magnitude, and duration of tumor control; overall survival (OS); health-related quality of life (HRQL); changes in subject performance status; disease-associated biomarkers and potential mechanisms of resistance; treatment administration; safety; and health resource utilization.

Main Objective: • To evaluate the effect of Idelalisib(formerly GS-1101) on the onset, magnitude, and duration of tumor control
• To compare tumor control in subjects receiving rituximab alone in Study GS-US-312-0116 to that observed in the same subjects when receiving the standard dose of idelalisib alone in Study GS US 312 0117
• To assess the effect of idelalisib on measures of subject well-being, including overall survival (OS), health related quality of life (HRQL), and performance status
• To assess the effects of idelalisib on disease associated biomarkers and to evaluate potential mechanisms of resistance to idelalisib
• To characterize exposure to idelalisib as determined by treatment administration and evaluation of GS-1101 plasma concentrations over time
• To describe the safety profile observed with idelalisib
• To estimate health resource utilization associated with administration of idelalisib

Timepoint(s) of evaluation of this end point: every 8-12 weeks

Primary end point(s): -Tumour control
-Patient well-being
-Pharmacodynamic Markers of drug activity and resistance
-exposure
-Safety
-Pharmacoeconomics

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: every 8-12 weeks

Secondary end point(s): Tumour control
-Progression-free survival (PFS)
-Overall response rate (ORR)
-Lymph node response rate
-CR rate
-Time to response (TTR)
-Duration of response (DOR)
-Percentage change in lymph node area
-Splenomegaly response rate
-Hepatomegaly response rate
-ALC response rate
-Platelet response rate
-Hemoglobin response rate
-Neutrophil response rate

Patient Well-being
• Overall survival (OS)
• Change from baseline in HRQL domain and symptom scores based on
the Functional
Assessment of Cancer Therapy: Leukemia (FACT-Leu)
• Changes from baseline in Karnofsky performance status

Pharmacodynamic Markers of Drug Activity and Resistance
• Changes from baseline in PI3K/AKT/mTOR pathway activation as a
measure of PI3Kd pathway activity
• Changes from baseline in the plasma concentrations of diseaseassociated
chemokines and cytokines

Exposure
• Study drug administration as assessed by prescribing records and
compliance as assessed
by quantification of used and unused drug
• Trough (pre-dose) and peak (1.5-hour samples) of idelalisib plasma
concentrations as
assessed by a validated bioanalytical method

Safety
Overall safety profile of each study treatment regimen characterized by
the type,
frequency, severity, timing of onset, duration, and relationship to study
therapy of any
adverse events or abnormalities of laboratory tests; serious adverse
events; or adverse
events leading to discontinuation of study drug

Pharmacoeconomics
-Change in health status – defined as the change from baseline in overall
health and
single-item dimension scores as assessed using the EuroQoL Five-
Dimension (EQ-5D)
utility measure
-Health resource measures, including resource utilization, total costs,
and measures of cost
per unit of benefit (eg, cost per additional progression-free month, cost
per
quality-adjusted life-year)

Secondary ID(s)

GS-US-312-0117

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 14/07/2019
• Date Completed: 29/06/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-006293-72/results