Chronic Lymphocytic Leukemia, Lymphoma, Non-Hodgkin
Conditions
Keywords
Idelalisib, Chronic lymphocytic leukemia (CLL), Non-Hodgkin lymphoma (NHL), Phosphatidylinositol 3-kinase (PI3K)
Brief summary
This is a long-term safety extension study of idelalisib (GS-1101; CAL-101) in patients with hematologic malignancies who complete other idelalisib studies. It provides the opportunity for patients to continue treatment as long as the patient is deriving clinical benefit. Patients will be followed according to the standard of care as appropriate for their type of cancer. The dose of idelalisib will generally be the same as the dose that was administered at the end of the prior study, but may be titrated up to improve clinical response or down for toxicity. Patients will be withdrawn from the study if they develop progressive disease, unacceptable toxicity related to idelalisib, or if they no longer derive clinical benefit in the opinion of the investigator.
Interventions
DRUGIdelalisib
Idelalisib tablets or capsules administered orally
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: * Patients with hematologic malignancies completing a prior idelalisib study with a clinical benefit are eligible * Women of childbearing potential must have a negative pregnancy test to be eligible * Male patients, and female patients of childbearing potential, must agree to use method(s) of contraception specified in the protocol Key
Exclusion criteria
* Patients who are unwilling or unable to comply with the protocol are not eligible Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) | Overall response rate (ORR) was defined as the percentage of participants who achieve complete response (CR), partial response (PR), or minor response (MR; for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) only). |
| Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events | Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) plus 30 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) | Duration of response (DOR) was defined as the interval from the first documentation of CR, PR, or MR (for LPL/WM) to the earlier of the first documentation of disease progression or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates. |
| Progression-Free Survival | Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) | Progression-free survival (PFS) was defined as the interval from start of idelalisib treatment in the parent study to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using KM estimates. |
| Overall Survival | Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) | Overall survival (OS) was defined as the interval from the start of study treatment in the parent study to death from any cause. OS was analyzed using KM estimates. |
| Time to Response | Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) | Time to response (TTR) was defined as the interval from start of study treatment to the first documentation of CR, PR, or MR (for LPL/WM). Analysis only includes participants who achieved complete or partial response (or minor response for LPL/WM participants). No participants in the 101-02 (AML and MM) groups achieved a complete or partial response. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 22 March 2010. The last study visit occurred on 18 June 2018.
Pre-assignment details
Participants must have been enrolled in a previous Gilead-sponsored study.
Participants by arm
| Arm | Count |
|---|---|
| 101-02 Participants with CLL, iNHL, MCL, DLBCL, AML, or MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. | 191 |
| 101-07 Participants with CLL, iNHL, or MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, everolimus, bortezomib, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. | 241 |
| 101-08 Participants with CLL or iNHL (specifically, small lymphocytic lymphoma (SLL)) received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. | 64 |
| 101-10 Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment. | 18 |
| Total | 514 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Study 101-99 | Adverse Event | 10 | 28 | 18 | 0 |
| Study 101-99 | Death | 3 | 8 | 1 | 0 |
| Study 101-99 | Investigator Request | 1 | 11 | 4 | 0 |
| Study 101-99 | Other (Unknown Reasons) | 3 | 3 | 0 | 0 |
| Study 101-99 | Participant Request | 3 | 1 | 0 | 0 |
| Study 101-99 | Progressive Disease | 28 | 48 | 10 | 4 |
| Study 101-99 | Sponsor Discontinued Study | 0 | 7 | 5 | 0 |
| Study 101-99 | Withdrew Consent | 0 | 2 | 3 | 1 |
Baseline characteristics
| Characteristic | Total | 101-10 | 101-02 | 101-08 | 101-07 |
|---|---|---|---|---|---|
| Age, Customized < 65 years | 215 Participants | 13 Participants | 86 Participants | 0 Participants | 116 Participants |
| Age, Customized ≥ 65 years | 299 Participants | 5 Participants | 105 Participants | 64 Participants | 125 Participants |
| Diagnosis Status Acute myeloid leukemia (AML) | 12 Participants | 0 Participants | 12 Participants | 0 Participants | 0 Participants |
| Diagnosis Status Chronic lymphocytic leukemia (CLL) | 228 Participants | 0 Participants | 54 Participants | 59 Participants | 115 Participants |
| Diagnosis Status Diffuse large B-cell lymphoma (DLBCL) | 9 Participants | 0 Participants | 9 Participants | 0 Participants | 0 Participants |
| Diagnosis Status Indolent non-Hodgkin lymphoma (iNHL) | 172 Participants | 17 Participants | 64 Participants | 5 Participants | 86 Participants |
| Diagnosis Status Mantle cell lymphoma (MCL) | 80 Participants | 0 Participants | 40 Participants | 0 Participants | 40 Participants |
| Diagnosis Status Missing | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Diagnosis Status Multiple myeloma (MM) | 12 Participants | 0 Participants | 12 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 482 Participants | 17 Participants | 167 Participants | 64 Participants | 234 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 25 Participants | 0 Participants | 22 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Asian | 14 Participants | 1 Participants | 1 Participants | 1 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Black or African American | 21 Participants | 5 Participants | 6 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Not Reported | 33 Participants | 0 Participants | 22 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Other | 4 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 442 Participants | 12 Participants | 160 Participants | 61 Participants | 209 Participants |
| Sex: Female, Male Female | 160 Participants | 8 Participants | 52 Participants | 24 Participants | 76 Participants |
| Sex: Female, Male Male | 354 Participants | 10 Participants | 139 Participants | 40 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 25 / 191 | 36 / 241 | 7 / 45 | 2 / 6 |
| other Total, other adverse events | 183 / 191 | 236 / 241 | 63 / 64 | 16 / 18 |
| serious Total, serious adverse events | 100 / 191 | 165 / 241 | 45 / 64 | 6 / 18 |
Outcome results
Primary
Overall Response Rate
Overall response rate (ORR) was defined as the percentage of participants who achieve complete response (CR), partial response (PR), or minor response (MR; for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) only).
Time frame: Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Population: Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 101-02 (AML) | Overall Response Rate | 0 percentage of participants |
| 101-02 (CLL) | Overall Response Rate | 57.4 percentage of participants |
| 101-02 (DLBCL) | Overall Response Rate | 11.1 percentage of participants |
| 101-02 (iNHL) | Overall Response Rate | 48.4 percentage of participants |
| 101-02 (MCL) | Overall Response Rate | 40.0 percentage of participants |
| 101-02 (MM) | Overall Response Rate | 0 percentage of participants |
| 101-07 (CLL) | Overall Response Rate | 81.7 percentage of participants |
| 101-07 (iNHL) | Overall Response Rate | 82.6 percentage of participants |
| 101-07 (MCL) | Overall Response Rate | 57.5 percentage of participants |
| 101-08 (CLL or SLL) | Overall Response Rate | 96.9 percentage of participants |
| 101-10 (iNHL) | Overall Response Rate | 44.4 percentage of participants |
Primary
Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events
Time frame: Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) plus 30 days
Population: Data presented includes data from both the parent studies and this Study 101-99. For this safety endpoint, data was prespecified to be combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 101-02 (AML) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events | 98.4 percentage of participants |
| 101-02 (CLL) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events | 98.8 percentage of participants |
| 101-02 (DLBCL) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events | 100.0 percentage of participants |
| 101-02 (iNHL) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events | 94.4 percentage of participants |
Secondary
Duration of Response
Duration of response (DOR) was defined as the interval from the first documentation of CR, PR, or MR (for LPL/WM) to the earlier of the first documentation of disease progression or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.
Time frame: Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Population: Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 101-02 (AML) | Duration of Response | NA Months |
| 101-02 (CLL) | Duration of Response | 21.2 Months |
| 101-02 (DLBCL) | Duration of Response | NA Months |
| 101-02 (iNHL) | Duration of Response | 18.4 Months |
| 101-02 (MCL) | Duration of Response | 2.7 Months |
| 101-02 (MM) | Duration of Response | NA Months |
| 101-07 (CLL) | Duration of Response | 26.6 Months |
| 101-07 (iNHL) | Duration of Response | 42.9 Months |
| 101-07 (MCL) | Duration of Response | 9.3 Months |
| 101-08 (CLL or SLL) | Duration of Response | 63.8 Months |
| 101-10 (iNHL) | Duration of Response | 14.4 Months |
Secondary
Overall Survival
Overall survival (OS) was defined as the interval from the start of study treatment in the parent study to death from any cause. OS was analyzed using KM estimates.
Time frame: Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Population: Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 101-02 (AML) | Overall Survival | NA Months |
| 101-02 (CLL) | Overall Survival | NA Months |
| 101-02 (DLBCL) | Overall Survival | NA Months |
| 101-02 (iNHL) | Overall Survival | NA Months |
| 101-02 (MCL) | Overall Survival | NA Months |
| 101-02 (MM) | Overall Survival | 5.2 Months |
| 101-07 (CLL) | Overall Survival | NA Months |
| 101-07 (iNHL) | Overall Survival | NA Months |
| 101-07 (MCL) | Overall Survival | NA Months |
| 101-08 (CLL or SLL) | Overall Survival | NA Months |
| 101-10 (iNHL) | Overall Survival | NA Months |
Secondary
Progression-Free Survival
Progression-free survival (PFS) was defined as the interval from start of idelalisib treatment in the parent study to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using KM estimates.
Time frame: Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Population: Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 101-02 (AML) | Progression-Free Survival | 0.9 Months |
| 101-02 (CLL) | Progression-Free Survival | 15.8 Months |
| 101-02 (DLBCL) | Progression-Free Survival | 1.5 Months |
| 101-02 (iNHL) | Progression-Free Survival | 7.6 Months |
| 101-02 (MCL) | Progression-Free Survival | 3.7 Months |
| 101-02 (MM) | Progression-Free Survival | 1 Months |
| 101-07 (CLL) | Progression-Free Survival | 26.1 Months |
| 101-07 (iNHL) | Progression-Free Survival | 32.8 Months |
| 101-07 (MCL) | Progression-Free Survival | 11.1 Months |
| 101-08 (CLL or SLL) | Progression-Free Survival | 65.6 Months |
| 101-10 (iNHL) | Progression-Free Survival | 10.2 Months |
Secondary
Time to Response
Time to response (TTR) was defined as the interval from start of study treatment to the first documentation of CR, PR, or MR (for LPL/WM). Analysis only includes participants who achieved complete or partial response (or minor response for LPL/WM participants). No participants in the 101-02 (AML and MM) groups achieved a complete or partial response.
Time frame: Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Population: Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 101-02 (CLL) | Time to Response | 1.9 Months |
| 101-02 (DLBCL) | Time to Response | 4.0 Months |
| 101-02 (iNHL) | Time to Response | 1.3 Months |
| 101-02 (MCL) | Time to Response | 1.1 Months |
| 101-07 (CLL) | Time to Response | 1.9 Months |
| 101-07 (iNHL) | Time to Response | 1.9 Months |
| 101-07 (MCL) | Time to Response | 1.9 Months |
| 101-08 (CLL or SLL) | Time to Response | 1.9 Months |
| 101-10 (iNHL) | Time to Response | 2.7 Months |