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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01980875




Registration number
NCT01980875
Ethics application status
Date submitted
5/11/2013
Date registered
11/11/2013
Date last updated
19/11/2018

Titles & IDs
Public title
Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
Scientific title
A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
Secondary ID [1] 0 0
2013-004551-20
Secondary ID [2] 0 0
GS-US-312-0118
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Idelalisib
Treatment: Drugs - Chlorambucil
Treatment: Drugs - Obinutuzumab

Experimental: Safety Run-In: Idelalisib+obinutuzumab - Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Following 4 weeks of treatment, safety data will be reviewed by an independent data monitoring committee (DMC). If acceptable tolerability is observed, the randomized portion of the study will begin.

Experimental: Randomized: Idelalisib+obinutuzumab - Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.

Active Comparator: Randomized: Obinutuzumab+chlorambucil - Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.


Treatment: Drugs: Idelalisib
150 mg tablet administered orally twice daily

Treatment: Drugs: Chlorambucil
2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses

Treatment: Drugs: Obinutuzumab
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival - Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone. PFS was to be assessed by an independent review committee (IRC).
Timepoint [1] 0 0
Up to 11 months
Secondary outcome [1] 0 0
Overall Response Rate - Overall response rate (ORR) is defined as the proportion of participants who achieve a confirmed complete or partial response. ORR was to be assessed by an IRC.
Timepoint [1] 0 0
Up to 11 months
Secondary outcome [2] 0 0
Nodal Response Rate - Nodal response rate is defined as the proportion of participants who achieve a 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Nodal response rate was to be assessed by an IRC.
Timepoint [2] 0 0
Up to 11 months
Secondary outcome [3] 0 0
Complete Response Rate - Complete response rate is defined as the proportion of participants who achieve a confirmed complete response. Complete response rate was to be assessed by an IRC.
Timepoint [3] 0 0
Up to 11 months
Secondary outcome [4] 0 0
Overall Survival - Overall survival is defined as the interval from randomization to death from any cause. Overall survival was to be assessed by an IRC.
Timepoint [4] 0 0
Up to 11 months
Secondary outcome [5] 0 0
Minimal Residual Disease Negativity Rate at Week 36 - Minimal residual disease (MRD) negativity rate is defined as the proportion of participants with MRD < 10^-4 assessed by flow cytometry in bone marrow at Week 36 after therapy initiation. For participants receiving the final dose of obinutuzumab after the original scheduled date, the MRD assessment was performed no less than 12 weeks after the last dose of obinutuzumab. MRD negativity rate was to be assessed by an IRC.
Timepoint [5] 0 0
Up to 11 months

Eligibility
Key inclusion criteria
Key

- Not a candidate for fludarabine therapy based on either:

1. creatinine clearance < 70 mL/min, or

2. Cumulative Illness Rating Scale score > 6, by assessment of the investigator

- Diagnosis of B-cell CLL, with diagnosis established according to International
Workshop on Chronic Lymphocytic Leukemia (IWCLL)

- No prior therapy for CLL other than corticosteroids for disease complications.

- CLL that warrants treatment

- Presence of measurable lymphadenopathy

- Eastern Cooperative Oncology Group (ECOG) performance status of = 2

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known histological transformation from CLL to an aggressive lymphoma (ie, Richter
transformation)

- Known presence of myelodysplastic syndrome

- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of
randomization

- Ongoing liver injury

- Ongoing drug-induced pneumonitis

- Ongoing inflammatory bowel disease

- History of prior allogeneic bone marrow progenitor cell or solid organ transplantation

- Ongoing immunosuppressive therapy other than corticosteroids

- Concurrent participation in another therapeutic clinical trial

- Undergone major surgery within 30 days prior to randomization

- Known hypersensitivity or intolerance to any of the active substances or excipients in
the formulations for idelalisib, obinutuzumab, or chlorambucil

- History of non-infectious pneumonitis

- Received last dose of study drug on another therapeutic clinical trial within 30 days
prior to randomization

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent Hospital, Sydney - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
South Carolina
Country [5] 0 0
Belgium
State/province [5] 0 0
Ghent
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
France
State/province [7] 0 0
Le Mans
Country [8] 0 0
France
State/province [8] 0 0
Perpignan Cedex 9
Country [9] 0 0
Poland
State/province [9] 0 0
Podkarpackie
Country [10] 0 0
Poland
State/province [10] 0 0
Krakow
Country [11] 0 0
Poland
State/province [11] 0 0
Legnica
Country [12] 0 0
Poland
State/province [12] 0 0
Lodz
Country [13] 0 0
Poland
State/province [13] 0 0
Olsztyn
Country [14] 0 0
Spain
State/province [14] 0 0
Salamanca
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Kent

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the effects of idelalisib with
obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free
survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).

An increased rate of deaths and serious adverse events (SAEs) among participants with
front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in
combination with standard therapies was observed by the independent data monitoring committee
(DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data
and terminated those studies in agreement with the DMC recommendation and in consultation
with the US Food and Drug Administration (FDA). All front-line studies of idelalisib,
including this study, were also terminated.
Trial website
https://clinicaltrials.gov/show/NCT01980875
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01980875