A Phase 2 interventional study of Idelalisib in Follicular Lymphoma, Small Lymphocytic Lymphoma and Lymphoplasmacytic Lymphoma, sponsored by Gilead Sciences. Completed at 41 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-07-11.
Sponsored by Gilead Sciences · Phase 2, Interventional, and Treatment
The primary objective will be to assess the overall response rate and to evaluate the efficacy and safety of idelalisib (IDELA; GS-1101) in participants with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy.
Eligible participants will initiate oral therapy with idelalisib at a starting dose of 150 mg taken twice per day. Treatment with idelalisib can continue in compliant participants as long as the study is still ongoing and the participants appear to be benefiting from treatment with acceptable safety.
5,577 studies on the registry are indexed under Lymphoma; 824 are open to participants now.
This study's enrollment of 125 is above the median of 40 across 4,507 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.
Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:
Key Exclusion Criteria:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Treatment with idelalisib will be continued until tumor progression or development of unacceptable toxicity.
Drug: Idelalisib
Idelalisib 150 mg tablet administered orally twice daily
Also known as: Zydelig®, GS-1101, CAL-101, IDELA
Overall Response Rate
Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) or partial response (PR; or minor response \[MR\] for participants with WM) as assessed by the study independent review committee (IRC). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. For WM only, response was defined as a reduction in immunoglobulin M (IgM) of ≥ 50% decrease for PR, and ≥ 25% decrease for MR; no increase from baseline in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions or signs and symptoms of active disease (Owen, 2013)
Time frame: Start of Treatment to End of Treatment (up to 81 months)
Duration of Response
Duration of Response (DOR) was defined as the interval from the first documentation of CR or PR (or MR for participants with WM) to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.
Time frame: Start of Treatment to End of Treatment (up to 81 months)
Lymph Node Response Rate
Lymph node response (LNR) was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions as assessed by the study IRC.
Time frame: Start of Treatment to End of Treatment (up to 81 months)
Time to Response
Time to response (TTR) was defined as the interval from the start of idelalisib treatment to the first documentation of CR or PR (or MR for participants with WM) as assessed by the study IRC.
Time frame: Start of Treatment to End of Treatment (up to 81 months)
Progression-Free Survival
Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. PFS was analyzed using KM estimates.
Time frame: Start of Treatment to End of Treatment (up to 81 months)
Overall Survival
Overall survival (OS) was defined as the time interval from the start of idelalisib treatment to death from any cause. OS was analyzed using KM estimates.
Time frame: Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)
Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS)
Change in health-related quality of life events were reported by participants using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) assessment tool. Results are presented as the mean (SD) best change from baseline. The best change from baseline was defined as the highest change score (improvement) after baseline. The FACT-LymS is on a scale from 0-60, with higher scores associated with a better quality of life. It incorporates values from 15 questions, each rated 0-4, related to study indications.
Time frame: Baseline to End of Treatment (up to 81 months)
Change in Karnofsky Performance Status
The change in Karnofsky performance status was reported as the best (highest change score) and worst (lowest change score) change from baseline using the Karnofsky performance criteria. The Karnofsky score classified participants according to their functional impairment. Scores are on a scale from 0-100, the lower the score, the worse the survival for most serious illnesses.
Time frame: Baseline to End of Treatment (up to 81 months)
Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines
Analysis of the cytokine/chemokine was planned to be performed on a subset of samples from this study along with a subset of samples from other studies. Therefore, data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time frame: Enrollment to End of Treatment (up to 81 months)
Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms
This composite endpoint measured the safety and tolerability profile of idelalisib. "Clinically meaningful" abnormalities in vital signs and electrocardiograms (ECG) were as determined by the investigator.
Time frame: Start of Treatment to End of Treatment (up to 81 months) plus 30 days
Study Drug Exposure
The average idelalisib exposure was summarized.
Time frame: Start of Treatment to End of Treatment (up to 81 months)
Idelalisib Plasma Concentration
Time frame: Predose and at 1.5 hours (± 5 minutes) postdose on Day 29
PK Parameter: Cmax
Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
PK Parameter: Tmax
Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
PK Parameter: AUClast
AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29
Participants were enrolled at a total of 54 study sites in North America and Europe. The first participant was screened on 04 March 2011. The last participant observation was on 16 May 2018.
| Milestone | Idelalisib |
|---|---|
| Started | 125 |
| Completed: disease progression | 70 |
| Completed: death | 9 |
| Completed | 79 |
| Not completed | 46 |
| Withdrew: Adverse event | 30 |
| Withdrew: Withdrew consent | 6 |
| Withdrew: Investigator request | 7 |
| Withdrew: Other (unknown) | 3 |
| Milestone | Idelalisib |
|---|---|
| Started | 84 |
| Completed | 20 |
| Not completed | 64 |
| Withdrew: Withdrew consent | 2 |
| Withdrew: Death | 40 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Other (unknown) | 21 |
Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) or partial response (PR; or minor response \[MR\] for participants with WM) as assessed by the study independent review committee (IRC). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. For WM only, response was defined as a reduction in immunoglobulin M (IgM) of ≥ 50% decrease for PR, and ≥ 25% decrease for MR; no increase from baseline in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions or signs and symptoms of active disease (Owen, 2013)
| percentage of participants | Idelalisib |
|---|---|
| Overall Response Rate | 57.6 (48.4 to 66.4) |
Duration of Response (DOR) was defined as the interval from the first documentation of CR or PR (or MR for participants with WM) to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.
| months | Idelalisib |
|---|---|
| Duration of Response | 12.5 (6.2 to 28.6) |
Lymph node response (LNR) was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions as assessed by the study IRC.
| percentage of participants | Idelalisib |
|---|---|
| Lymph Node Response Rate | 56.8 (47.6 to 65.6) |
Time to response (TTR) was defined as the interval from the start of idelalisib treatment to the first documentation of CR or PR (or MR for participants with WM) as assessed by the study IRC.
| months | Idelalisib |
|---|---|
| Time to Response | 2.0 (1.8 to 4.2) |
Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. PFS was analyzed using KM estimates.
| months | Idelalisib |
|---|---|
| Progression-Free Survival | 11.1 (8.3 to 14.0) |
Overall survival (OS) was defined as the time interval from the start of idelalisib treatment to death from any cause. OS was analyzed using KM estimates.
| months | Idelalisib |
|---|---|
| Overall Survival | 48.6 (33.9 to 71.7) |
Change in health-related quality of life events were reported by participants using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) assessment tool. Results are presented as the mean (SD) best change from baseline. The best change from baseline was defined as the highest change score (improvement) after baseline. The FACT-LymS is on a scale from 0-60, with higher scores associated with a better quality of life. It incorporates values from 15 questions, each rated 0-4, related to study indications.
| units on a scale | Idelalisib |
|---|---|
| Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) | 10.3 ± 17.08 |
The change in Karnofsky performance status was reported as the best (highest change score) and worst (lowest change score) change from baseline using the Karnofsky performance criteria. The Karnofsky score classified participants according to their functional impairment. Scores are on a scale from 0-100, the lower the score, the worse the survival for most serious illnesses.
| units on a scale | Idelalisib |
|---|---|
| Best change | 3.0 ± 8.71 |
| Worst change | -10.7 ± 12.61 |
Analysis of the cytokine/chemokine was planned to be performed on a subset of samples from this study along with a subset of samples from other studies. Therefore, data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Results for this outcome have not been posted.
This composite endpoint measured the safety and tolerability profile of idelalisib. "Clinically meaningful" abnormalities in vital signs and electrocardiograms (ECG) were as determined by the investigator.
| Participants | Idelalisib |
|---|---|
| Any AE | 123 |
| AE leading to drug discontinuation | 35 |
| Serious AE | 72 |
| Vital signs abnormal - clinically meaningful | 0 |
| ECG abnormal - clinically meaningful | 0 |
| Grade 3 or 4 hemoglobin | 2 |
| Grade 3 or 4 neutrophils | 35 |
| Grade 3 or 4 platelets | 9 |
| Grade 3 or 4 alanine aminotransferase | 16 |
| Grade 3 or 4 aspartate aminotransferase | 11 |
The average idelalisib exposure was summarized.
| months | Idelalisib |
|---|---|
| Study Drug Exposure | 13.2 ± 15.08 |
| ng/mL | Idelalisib |
|---|---|
| Predose | 471.6 ± 486.53 |
| Postdose | 2187.7 ± 1050.76 |
Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.
| ng/mL | Idelalisib |
|---|---|
| Cmax at Day 1 | 2647.5 ± 1084.99 |
| Cmax at Day 29 | 2258.8 ± 809.61 |
Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).
| hours | Idelalisib |
|---|---|
| Tmax at Day 1 | 1.00 (0.99 to 1.04) |
| Tmax at Day 29 | 1.00 (0.95 to 2.00) |
AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration
| hours x ng/mL | Idelalisib |
|---|---|
| AUClast at Day 1 | 9094.76 ± 2960.391 |
| AUClast at Day 29 | 9293.39 ± 3996.826 |
Collected over Adverse Events: Start of Treatment to End of Treatment (up to 81 months) plus 30 days; All-Cause Mortality: Baseline to Last Long-Term Follow-Up Visit (up to maximum of 7 years). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Idelalisib | 64/125 (51.2%) | 72/125 (57.6%) | 123/125 (98.4%) |
| Event | Idelalisib |
|---|---|
| PyrexiaGeneral disorders | 15/125 |
| PneumoniaInfections and infestations | 15/125 |
| DiarrhoeaGastrointestinal disorders | 11/125 |
| Febrile neutropeniaBlood and lymphatic system disorders | 5/125 |
| ColitisGastrointestinal disorders | 5/125 |
| DehydrationMetabolism and nutrition disorders | 4/125 |
| Acute kidney injuryRenal and urinary disorders | 4/125 |
| NeutropeniaBlood and lymphatic system disorders | 3/125 |
| Peripheral swellingGeneral disorders | 3/125 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 3/125 |
| Event | Idelalisib |
|---|---|
| DiarrhoeaGastrointestinal disorders | 59/125 |
| FatigueGeneral disorders | 40/125 |
| CoughRespiratory, thoracic and mediastinal disorders | 40/125 |
| NauseaGastrointestinal disorders | 38/125 |
| NeutropeniaBlood and lymphatic system disorders | 35/125 |
| PyrexiaGeneral disorders | 34/125 |
| ThrombocytopeniaBlood and lymphatic system disorders | 23/125 |
| Upper respiratory tract infectionInfections and infestations | 23/125 |
| Decreased appetiteMetabolism and nutrition disorders | 23/125 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 22/125 |
ITT analysis set included enrolled participants who received at least one dose of study drug.
| Age, Continuous(years) | Idelalisib |
|---|---|
| Mean | 62 ± 11.4 |
| Sex: Female, Male(Participants) | Idelalisib |
|---|---|
| Female | 45 |
| Male | 80 |
| Race/Ethnicity, Customized(Participants) | Idelalisib |
|---|---|
| Race — White/Caucasian | 110 |
| Race — Black or African American | 2 |
| Race — Asian | 3 |
| Race — American Indian or Alaska Native | 1 |
| Race — Other | 8 |
| Race — Missing | 1 |
| Race/Ethnicity, Customized(Participants) | Idelalisib |
|---|---|
| Ethnicity — Hispanic or Latino | 6 |
| Ethnicity — Not Hispanic or Latino | 117 |
| Ethnicity — Missing | 2 |
| Region of Enrollment(Participants) | Idelalisib |
|---|---|
| France | 10 |
| United States | 83 |
| Poland | 8 |
| Germany | 10 |
| United Kingdom | 8 |
| Italy | 6 |
| Karnofsky Performance Status(Participants) | Idelalisib |
|---|---|
| Score = 60 | 2 |
| Score = 70 | 6 |
| Score = 80 | 27 |
| Score = 90 | 44 |
| Score = 100 | 46 |
| Baseline Disease History(Participants) | Idelalisib |
|---|---|
| Folicular lymphoma | 72 |
| Small lymphocytic lymphoma | 28 |
| LPL/WM | 10 |
| Marginal zone lymphoma | 15 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Supporting information: Study protocol, Sap
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