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 : October 11, 2017

Sponsor:

Information provided by (Responsible Party):

Gilead Sciences

Study Description

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


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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Bendamustine hydrochloride Bendamustine Rituximab Idelalisib

Genetic and Rare Diseases Information Center resources: Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic

U.S. FDA Resources

Arms and Interventions

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

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

Primary Outcome Measures :

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 :

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.

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

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

Show 91 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators


Study Director:	Gilead Study Director	Gilead Sciences

More Information


Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01980888 History of Changes
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:	October 11, 2017
Last Verified:	September 2017


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:


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 Idelalisib	Rituximab Bendamustine Hydrochloride Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors

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