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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Idelalisib; Drug: Obinutuzumab; Drug: Chlorambucil

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent Hospital, Sydney
• Belgium
  • Ghent, Belgium, 9000
    • UZ Ghent- hematology
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre - Simcoe Musk
• France
  • Le Mans, France, 72037
    • Centre Hospitalier du Mans
  • Perpignan Cedex 9, France, 66046-BP 49954
    • Centre Hospitalier de Perpignan
• Poland
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne s.c.
  • Legnica, Poland, 59-220
    • Wojewodzki Szpital Specjalistyczny W Legnicy
  • Lodz, Poland, 93-510
    • Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego
  • Olsztyn, Poland, 10-228
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii
  • Podkarpackie
    • Brzozow, Podkarpackie, Poland, 36-200
      • Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej
• Spain
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
• United Kingdom
  • Kent
    • Canterbury, Kent, United Kingdom, CT1 3NG
      • East Kent Hospitals University NHS Foundation Trust
• United States
  • California
    • Santa Barbara, California, United States, 93105
      • Sansum Clinic
    • Santa Monica, California, United States, 90404
      • UCLA Jonsson Comprehensive Cancer Center
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • Cancer Center of Central Connecticut
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Idelalisib; 150 mg tablet administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101; Drug: Obinutuzumab; 1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
EXPERIMENTAL: Randomized: Idelalisib+obinutuzumab; Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.	Drug: Idelalisib; 150 mg tablet administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101; Drug: Obinutuzumab; 1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
ACTIVE_COMPARATOR: Randomized: Obinutuzumab+chlorambucil; Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.	Drug: Obinutuzumab; 1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks; Drug: Chlorambucil; 2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 21, 2015
• Primary Completion (ACTUAL): May 13, 2016
• Study Completion (ACTUAL): May 13, 2016

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (ESTIMATE): November 11, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 19, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Obinutuzumab; Chlorambucil; Idelalisib
• Other Study ID Numbers: GS-US-312-0118; 2013-004551-20 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No