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Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Adults With 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: NCT01980888
Recruitment Status : Terminated
First Posted : November 11, 2013
Results First Posted : October 11, 2017
Last Update Posted : November 19, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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Brief Summary:

The primary objective of this study is to evaluate the progression-free survival in participants with previously untreated chronic lymphocytic leukemia (CLL) who would otherwise be suitable for bendamustine and rituximab treatment as standard of care.

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 this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Idelalisib Drug: Bendamustine Drug: Rituximab Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 311 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Untreated Chronic Lymphocytic Leukemia
Actual Study Start Date : February 5, 2014
Actual Primary Completion Date : May 30, 2016
Actual Study Completion Date : June 16, 2016

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Idelalisib+bendamustine+rituximab
Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
 Drug: Idelalisib
150 mg tablet administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101

Drug: Bendamustine
Administered intravenously at a starting dose of 90 mg/m^2 for up to 6 cycles. Dosing will be based on mg/m^2 of body surface area.

Drug: Rituximab
Single-use vials administered intravenously weekly starting at 375 mg/m^2 on Day 1 (Week 0) and 500 mg/m^2 thereafter for a total of 6 infusions
Placebo Comparator: Placebo+bendamustine+rituximab
Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
 Drug: Bendamustine
Administered intravenously at a starting dose of 90 mg/m^2 for up to 6 cycles. Dosing will be based on mg/m^2 of body surface area.

Drug: Rituximab
Single-use vials administered intravenously weekly starting at 375 mg/m^2 on Day 1 (Week 0) and 500 mg/m^2 thereafter for a total of 6 infusions

Drug: Placebo
Placebo to match idelalisib administered orally twice daily


Outcome Measures
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Primary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: Up to 22 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 22 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 22 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 22 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 22 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 22 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 or at least 12 weeks after the last dose of rituximab or bendamustine (whichever is later) for participants receiving the final dose of rituximab after the original scheduled date. MRD negativity rate was to be assessed by an IRC.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Documented 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
  • History of non-infectious pneumonitis
  • Ongoing inflammatory bowel disease
  • History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
  • Ongoing immunosuppressive therapy other than corticosteroids
  • 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.

Contacts and Locations
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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): NCT01980888


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
More Information
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01980888    
Other Study ID Numbers: GS-US-312-0123
2013-003313-17 ( EudraCT Number )
First Posted: November 11, 2013    Key Record Dates
Results First Posted: October 11, 2017
Last Update Posted: November 19, 2018
Last Verified: September 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Rituximab
 Bendamustine Hydrochloride
Idelalisib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors