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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01980875
• Other study ID #: GS-US-312-0118
• Secondary ID: 2013-004551-20
• Status: Terminated
• Phase: Phase 3
• Start date: April 21, 2015
• Est. completion date: May 13, 2016

Study information

• Verified date: May 2017
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 57
• Est. completion date: May 13, 2016
• Est. primary completion date: May 13, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Idelalisib
150 mg tablet administered orally twice daily
• Chlorambucil
2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses
• Obinutuzumab
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks

Locations

Country	Name	City	State
Australia	St Vincent Hospital, Sydney	Darlinghurst	New South Wales
Belgium	UZ Ghent- hematology	Ghent
Canada	Royal Victoria Regional Health Centre - Simcoe Musk	Barrie	Ontario
France	Centre Hospitalier du Mans	Le Mans
France	Centre Hospitalier de Perpignan	Perpignan Cedex 9
Poland	Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej	Brzozow	Podkarpackie
Poland	Malopolskie Centrum Medyczne s.c.	Krakow
Poland	Wojewódzki Szpital Specjalistyczny w Legnicy	Legnica
Poland	Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego	Lodz
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii	Olsztyn
Spain	Hospital Universitario de Salamanca	Salamanca
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury	Kent
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Sansum Clinic	Santa Barbara	California
United States	UCLA Jonsson Comprehensive Cancer Center	Santa Monica	California
United States	Cancer Center of Central Connecticut	Southington	Connecticut
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Up to 11 months
Secondary	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.	Up to 11 months
Secondary	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.	Up to 11 months
Secondary	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.	Up to 11 months
Secondary	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.	Up to 11 months
Secondary	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.	Up to 11 months