Follicular Lymphoma, Indolent Non-Hodgkin's Lymphoma, Marginal Zone Lymphoma, Small Lymphocytic Lymphoma
Conditions
Keywords
Indolent Non-Hodgkin's Lymphoma, Non-Hodgkin Lymphoma, iNHL, NHL, CAL-101, PI3K, Phosphatidylinositol 3-kinase, Follicular Lymphoma (FL), Small Lymphocytic Lymphoma (SLL), Marginal Zone Lymphoma (MZL)
Brief summary
The primary objectives of this study is to evaluate the safety and efficacy of idelalisib (GS-1101, CAL-101) in participants with previously treated indolent non-Hodgkin lymphoma (iNHL). Eligible patients will initiate oral therapy with idelalisib at a starting dose of 150 mg twice per day. Treatment with idelalisib can continue in compliant participants for up to twelve 28-day cycles of idelalisib. Participants who appear to be benefiting from treatment at the completion of 12 cycles of treatment with idelalisib may be eligible for participation in a long-term safety extension study of idelalisib.
Interventions
DRUGIdelalisib
Tablet(s) administered orally twice daily
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
* Previously treated relapsed or refractory B-cell iNHL * Provide written informed consent
Exclusion criteria
* Pregnant or nursing * Active, serious infection requiring systemic therapy * Positive test for HIV antibodies * Active hepatitis B or C viral infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Safety of Idelalisib | 30 days post last study treatment (up to 12 months) | The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib). |
| Clinical Response: Overall Response Rate | Up to twelve 28-day cycles (maximum of 12 months) | Participants were assessed for clinical response by appropriate imaging at the end of cycles 3, 6, 9, and 12. Overall response rate (ORR) was assessed based on standardized criteria (Cheson 2007), and was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) based on investigator assessment after the start of idelalisib treatment until progression or the end of study drug treatment. * CR was defined as the disappearance of all evidence of disease. * PR was defined the regression of measurable disease and no new sites. |
Secondary
| Measure | Time frame |
|---|---|
| Flow Cytometric Measurement of Constitutive or Inducible Phosphorylation of Akt (at S473) and S6 Within Tumor B Cells | Up to twelve 28-day cycles (maximum of 12 months) |
| Flow Cytometric Measurement of Tumoral and Peripheral Blood T and NK Cells | Up to twelve 28-day cycles (maximum of 12 months) |
| Changes in Concentration of Peripheral Blood Chemokines and Cytokines | Up to twelve 28-day cycles (maximum of 12 months) |
| Changes in Liver Imaging as Assessed by Magnetic Resonance Imaging (MRI) and Gadoxetic Acid (GD-EOB-DTPA) Contrast | Up to twelve 28-day cycles (maximum of 12 months) |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 2 study sites in the United States. The first participant was screened on 22 February 2011. The last study visit occurred on 24 August 2015.
Pre-assignment details
24 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Idelalisib Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Disease Progression | 7 |
| Overall Study | Other: Change in Eligibility Status | 1 |
Baseline characteristics
| Characteristic | Idelalisib |
|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 12.6 |
| Diagnosis Follicular lymphoma | 10 participants |
| Diagnosis Marginal zone lymphoma | 3 participants |
| Diagnosis Missing | 1 participants |
| Diagnosis Small lymphocytic lymphoma | 4 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 18 |
| serious Total, serious adverse events | 5 / 18 |
Outcome results
Primary
Clinical Response: Overall Response Rate
Participants were assessed for clinical response by appropriate imaging at the end of cycles 3, 6, 9, and 12. Overall response rate (ORR) was assessed based on standardized criteria (Cheson 2007), and was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) based on investigator assessment after the start of idelalisib treatment until progression or the end of study drug treatment. * CR was defined as the disappearance of all evidence of disease. * PR was defined the regression of measurable disease and no new sites.
Time frame: Up to twelve 28-day cycles (maximum of 12 months)
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Idelalisib | Clinical Response: Overall Response Rate | 44.4 percentage of participants |
Primary
Overall Safety of Idelalisib
The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).
Time frame: 30 days post last study treatment (up to 12 months)
Population: Intent-to-treat (ITT) Analysis Set: all enrolled participants who received at least 1 dose of idelalisib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Idelalisib | Overall Safety of Idelalisib | Any AE | 88.9 percentage of participants |
| Idelalisib | Overall Safety of Idelalisib | Serious AE | 27.8 percentage of participants |
| Idelalisib | Overall Safety of Idelalisib | Grade ≥ 3 AE | 55.6 percentage of participants |
| Idelalisib | Overall Safety of Idelalisib | AE related to idelalisib | 83.3 percentage of participants |
| Idelalisib | Overall Safety of Idelalisib | AE leading to permanent drug discontinuation | 27.8 percentage of participants |
Secondary
Changes in Concentration of Peripheral Blood Chemokines and Cytokines
Time frame: Up to twelve 28-day cycles (maximum of 12 months)
Population: Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.
Secondary
Changes in Liver Imaging as Assessed by Magnetic Resonance Imaging (MRI) and Gadoxetic Acid (GD-EOB-DTPA) Contrast
Time frame: Up to twelve 28-day cycles (maximum of 12 months)
Population: Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.
Secondary
Flow Cytometric Measurement of Constitutive or Inducible Phosphorylation of Akt (at S473) and S6 Within Tumor B Cells
Time frame: Up to twelve 28-day cycles (maximum of 12 months)
Population: Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.
Secondary
Flow Cytometric Measurement of Tumoral and Peripheral Blood T and NK Cells
Time frame: Up to twelve 28-day cycles (maximum of 12 months)
Population: Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.