Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01980875
Recruitment Status : Terminated
First Posted : November 11, 2013
Results First Posted : June 28, 2017
Last Update Posted : November 19, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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.


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Idelalisib Drug: Chlorambucil Drug: Obinutuzumab Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Safety Run-In Phase: Single Group; Randomized Phase: Parallel
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 21, 2015
Actual Primary Completion Date : May 13, 2016
Actual Study Completion Date : May 13, 2016


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:
  • GS-1101
  • CAL-101
  • Zydelig®

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:
  • GS-1101
  • CAL-101
  • Zydelig®

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

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




Primary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: Up to 11 months ]
    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).


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 11 months ]
    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.

  2. Nodal Response Rate [ Time Frame: Up to 11 months ]
    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.

  3. Complete Response Rate [ Time Frame: Up to 11 months ]
    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.

  4. Overall Survival [ Time Frame: Up to 11 months ]
    Overall survival is defined as the interval from randomization to death from any cause. Overall survival was to be assessed by an IRC.

  5. Minimal Residual Disease Negativity Rate at Week 36 [ Time Frame: Up to 11 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01980875


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

Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01980875     History of Changes
Other Study ID Numbers: GS-US-312-0118
2013-004551-20 ( EudraCT Number )
First Posted: November 11, 2013    Key Record Dates
Results First Posted: June 28, 2017
Last Update Posted: November 19, 2018
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Idelalisib
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Obinutuzumab
Chlorambucil
Antineoplastic Agents, Immunological
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents