B-cell Chronic Lymphocytic Leukemia (CLL) With 17p Deletion
Conditions
Keywords
Chronic Lymphocytic Leukemia, CLL
Brief summary
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.
Interventions
DRUGIdelalisib
150 mg tablets administered orally twice daily
DRUGRituximab
375 mg/m\^2 administered intravenously once weekly x 8 weeks
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Australia, Austria, Belgium, Czechia, Denmark, France, Hungary, Italy, Poland, Portugal, Romania, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Australia, Europe, and the United States. The first participant was screened on 06 August 2014. The last study visit occurred on 17 May 2016.
Pre-assignment details
130 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Idelalisib + Rituximab Idelalisib 150 mg tablet twice daily + rituximab 375 mg/m\^2 intravenously once weekly for 8 weeks | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Initiation of Anti-Neoplastic Therapy | 2 |
| Overall Study | Investigator's Discretion | 10 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Study Terminated by Sponsor | 77 |
| Overall Study | Withdrew Consent | 3 |
Baseline characteristics
| Characteristic | Idelalisib + Rituximab |
|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 91 Participants |
| Race/Ethnicity, Customized Not Permitted | 5 Participants |
| Race/Ethnicity, Customized White | 94 Participants |
| Region of Enrollment Australia | 6 participants |
| Region of Enrollment Austria | 3 participants |
| Region of Enrollment Belgium | 2 participants |
| Region of Enrollment Czech Republic | 9 participants |
| Region of Enrollment Denmark | 1 participants |
| Region of Enrollment France | 7 participants |
| Region of Enrollment Hungary | 2 participants |
| Region of Enrollment Italy | 14 participants |
| Region of Enrollment Poland | 15 participants |
| Region of Enrollment Portugal | 2 participants |
| Region of Enrollment Romania | 4 participants |
| Region of Enrollment Spain | 7 participants |
| Region of Enrollment United Kingdom | 11 participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 98 / 102 |
| serious Total, serious adverse events | 46 / 102 |
Outcome results
Primary
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).
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
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.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
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.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
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.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
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.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
Overall Survival
Overall survival was defined as the interval from the start of study treatment to death from any cause.
Population: Due to the early termination of the study, efficacy data were not mature for all participants, and therefore the prespecified analyses were not conducted.
Secondary
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.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.