Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia

NCT ID: NCT01980875

Last Updated: 2018-11-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-21

Study Completion Date

2016-05-13

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Safety Run-In Phase: Single Group; Randomized Phase: Parallel
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Idelalisib

Intervention Type DRUG

150 mg tablet administered orally twice daily

Obinutuzumab

Intervention Type DRUG

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

Randomized: Idelalisib+obinutuzumab

Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.

Group Type EXPERIMENTAL

Idelalisib

Intervention Type DRUG

150 mg tablet administered orally twice daily

Obinutuzumab

Intervention Type DRUG

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

Randomized: Obinutuzumab+chlorambucil

Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.

Group Type ACTIVE_COMPARATOR

Chlorambucil

Intervention Type DRUG

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

Obinutuzumab

Intervention Type DRUG

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

Interventions

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Idelalisib

150 mg tablet administered orally twice daily

Intervention Type DRUG

Chlorambucil

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

Intervention Type DRUG

Obinutuzumab

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

Intervention Type DRUG

Other Intervention Names

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GS-1101 CAL-101 Zydelig®

Eligibility Criteria

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Inclusion Criteria

* 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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Sansum Clinic

Santa Barbara, California, United States

Site Status

UCLA Jonsson Comprehensive Cancer Center

Santa Monica, California, United States

Site Status

Innovative Clinical Research Institute

Whittier, California, United States

Site Status

Cancer Center of Central Connecticut

Southington, Connecticut, United States

Site Status

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status

Saint Francis Cancer Center

Greenville, South Carolina, United States

Site Status

St Vincent Hospital, Sydney

Darlinghurst, New South Wales, Australia

Site Status

UZ Ghent- hematology

Ghent, , Belgium

Site Status

Royal Victoria Regional Health Centre - Simcoe Musk

Barrie, Ontario, Canada

Site Status

Centre Hospitalier du Mans

Le Mans, , France

Site Status

Centre Hospitalier de Perpignan

Perpignan, , France

Site Status

Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej

Brzozów, Podkarpackie Voivodeship, Poland

Site Status

Malopolskie Centrum Medyczne s.c.

Krakow, , Poland

Site Status

Wojewódzki Szpital Specjalistyczny w Legnicy

Legnica, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego

Lodz, , Poland

Site Status

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii

Olsztyn, , Poland

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

East Kent Hospitals University NHS Foundation Trust

Canterbury, Kent, United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Poland Spain United Kingdom

Other Identifiers

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2013-004551-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-312-0118

Identifier Type: -

Identifier Source: org_study_id

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