Clinical trial NCT01980875: Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Safety Run-In Phase: Single Group; Randomized Phase: Parallel
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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

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.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: Up to 11 months
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Up to 11 months
measure: Nodal Response Rate
timeFrame: Up to 11 months
measure: Complete Response Rate
timeFrame: Up to 11 months
measure: Overall Survival
timeFrame: Up to 11 months
measure: Minimal Residual Disease Negativity Rate at Week 36
timeFrame: Up to 11 months
Other outcomes:
Locations:
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Santa Monica
country: United States
facility: UCLA Jonsson Comprehensive Cancer Center
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Southington
country: United States
facility: Cancer Center of Central Connecticut
state: Connecticut
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: Darlinghurst
country: Australia
facility: St Vincent Hospital, Sydney
state: New South Wales
city: Ghent
country: Belgium
facility: UZ Ghent- hematology
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre - Simcoe Musk
state: Ontario
city: Le Mans
country: France
facility: Centre Hospitalier du Mans
city: Perpignan Cedex 9
country: France
facility: Centre Hospitalier de Perpignan
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej
state: Podkarpackie
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne s.c.
city: Legnica
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Legnicy
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust
state: Kent
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: