Efficacy and Safety of Idelalisib in Combination With Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia With 17p Deletion

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate overall response rate (ORR) following treatment with idelalisib plus rituximab in participants with previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion. 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.

Official Title
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A Phase 2, Single Arm Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia With 17p Deletion

Conditions
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B-cell Chronic Lymphocytic Leukemia (CLL) With 17p Deletion

Intervention / Treatment
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* Drug: Idelalisib
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented diagnosis of B-cell CLL, according to International Workshop on Chronic Lymphocytic Leukemia 2008 Presence of 17p deletion in CLL cells as demonstrated by fluorescence in-situ hybridization (FISH) testing 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 History of a non-CLL malignancy except for the following: the malignancy has been in remission without treatment for ≥ 5 years prior to enrollment, or carcinoma in situ of the cervix, or adequately treated basal or squamous cell skin cancer or other localized non-melanoma skin cancer, or asymptomatic prostate cancer without known metastatic disease and with no current requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥ 1 year prior to enrollment, or ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone, or other adequately treated Stage 1 or 2 cancer currently in complete remission Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment Ongoing liver injury History of noninfectious 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 enrollment Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idelalisib + rituximab<br>Participants will receive rituximab for 8 weeks and Idelalisib continuously throughout the study (up to 10 years). | Drug: Idelalisib<br>* 150 mg tablets administered orally twice daily<br>* Other names: Zydelig®;Drug: Rituximab<br>* 375 mg/m^2 administered intravenously once weekly x 8 weeks<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate (ORR) was defined as the proportion of participants who achieve a confirmed complete or partial response. ORR was to be assessed by an independent review committee (IRC). |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration of response (DOR) was defined as the interval from the first documentation of confirmed complete response or partial response (by IRC) to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is chronic lymphocytic leukemia (CLL) progression based on standard criteria, excluding lymphocytosis alone. |  | 
| Nodal Response Rate | Nodal response rate was 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 | Complete response rate was defined as the proportion of participants who achieve a confirmed complete response. Complete response rate was to be assessed by an IRC. |  | 
| Progression-Free Survival | Progression-free survival (PFS) was defined as the interval from first dose of study drug 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 IRC. |  | 
| Overall Survival | Overall survival was defined as the interval from the start of study treatment to death from any cause. |  | 
| Minimal Residual Disease Negativity Rate at Week 36 | Minimal residual disease (MRD) negativity rate was 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 rituximab after the original scheduled date, the MRD assessment will be performed no fewer than 12 weeks after the last dose of rituximab. |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Chronic Lymphocytic Leukemia