Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Adults With Previously Untreated Chronic Lymphocytic Leukemia
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ClinicalTrials.gov Identifier: NCT01980888 |
Recruitment Status :
Terminated
First Posted : November 11, 2013
Results First Posted : October 11, 2017
Last Update Posted : November 19, 2018
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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 |
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Chronic Lymphocytic Leukemia | Drug: Idelalisib Drug: Bendamustine Drug: Rituximab Drug: Placebo | Phase 3 |
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 |

Arm | Intervention/treatment |
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Experimental: Idelalisib+bendamustine+rituximab
Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
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Drug: Idelalisib
150 mg tablet administered orally twice daily
Other Names:
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.
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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 |
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.

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

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

Study Director: | Gilead Study Director | Gilead Sciences |
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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |