Brief Summary
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.
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.
Brief Title
Efficacy and Safety Study of Idelalisib in Participants With Indolent B-Cell Non-Hodgkin Lymphomas
Categories
Completion Date
Completion Date Type
Actual
Conditions
Follicular Lymphoma
Small Lymphocytic Lymphoma
Lymphoplasmacytic Lymphoma
Marginal Zone Lymphoma
Eligibility Criteria
Key Inclusion Criteria:
* Karnofsky performance status of ≥ 60 (Eastern Cooperative Oncology Group \[ECOG\] performance score of 0, 1, or 2)
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:
* Follicular lymphoma (FL)
* Small lymphocytic lymphoma (SLL) with absolute lymphocyte count \< 5 x 10\^9/L at the time of diagnosis and on baseline laboratory assessment performed within 4 weeks prior to the start of study drug administration
* Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)
* Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)
* Prior treatment with ≥ 2 prior chemotherapy-based or immunotherapy-based regimens for iNHL
* Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
* Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL
* Lymphoma that is refractory to rituximab and to an alkylating agent
* Discontinuation of all other therapies for treatment of iNHL ≥ 3 weeks before Visit 2
* For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods
* Willingness and ability to provide written informed consent and to comply with the protocol requirements
Key Exclusion Criteria:
* Central nervous system or leptomeningeal lymphoma
* Known histological transformation from iNHL to diffuse large B-cell lymphoma
* History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years
* Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment
* Pregnancy or breastfeeding
* Ongoing alcohol or drug addiction
* Known history of drug-induced liver injury, chronic active hepatitis B infection, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension
* History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
* Ongoing immunosuppressive therapy, including systemic corticosteroids. Participant may be using topical or inhaled corticosteroids.
* Prior therapy with idelalisib
* Exposure to another investigational drug within 3 weeks prior to start of study treatment
* Concurrent participation in another therapeutic treatment trial
* Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, alter the absorption, distribution, metabolism or excretion of the study drug, or impair the assessment of study results
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* Karnofsky performance status of ≥ 60 (Eastern Cooperative Oncology Group \[ECOG\] performance score of 0, 1, or 2)
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:
* Follicular lymphoma (FL)
* Small lymphocytic lymphoma (SLL) with absolute lymphocyte count \< 5 x 10\^9/L at the time of diagnosis and on baseline laboratory assessment performed within 4 weeks prior to the start of study drug administration
* Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)
* Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)
* Prior treatment with ≥ 2 prior chemotherapy-based or immunotherapy-based regimens for iNHL
* Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
* Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL
* Lymphoma that is refractory to rituximab and to an alkylating agent
* Discontinuation of all other therapies for treatment of iNHL ≥ 3 weeks before Visit 2
* For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods
* Willingness and ability to provide written informed consent and to comply with the protocol requirements
Key Exclusion Criteria:
* Central nervous system or leptomeningeal lymphoma
* Known histological transformation from iNHL to diffuse large B-cell lymphoma
* History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years
* Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment
* Pregnancy or breastfeeding
* Ongoing alcohol or drug addiction
* Known history of drug-induced liver injury, chronic active hepatitis B infection, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension
* History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
* Ongoing immunosuppressive therapy, including systemic corticosteroids. Participant may be using topical or inhaled corticosteroids.
* Prior therapy with idelalisib
* Exposure to another investigational drug within 3 weeks prior to start of study treatment
* Concurrent participation in another therapeutic treatment trial
* Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, alter the absorption, distribution, metabolism or excretion of the study drug, or impair the assessment of study results
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Karnofsky performance status of ≥ 60 (Eastern Cooperative Oncology Group \[ECOG\] performance score of 0, 1, or 2)
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:
* Follicular lymphoma (FL)
* Small lymphocytic lymphoma (SLL) with absolute lymphocyte count \< 5 x 10\^9/L at the time of diagnosis and on baseline laboratory assessment performed within 4 weeks prior to the start of study drug administration
* Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)
* Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)
* Prior treatment with ≥ 2 prior chemotherapy-based or immunotherapy-based regimens for iNHL
* Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
* Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL
* Lymphoma that is refractory to rituximab and to an alkylating agent
* Discontinuation of all other therapies for treatment of iNHL ≥ 3 weeks before Visit 2
* For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods
* Willingness and ability to provide written informed consent and to comply with the protocol requirements
Inclusion/
* Karnofsky performance status of ≥ 60 (Eastern Cooperative Oncology Group \[ECOG\] performance score of 0, 1, or 2)
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:
* Follicular lymphoma (FL)
* Small lymphocytic lymphoma (SLL) with absolute lymphocyte count \< 5 x 10\^9/L at the time of diagnosis and on baseline laboratory assessment performed within 4 weeks prior to the start of study drug administration
* Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)
* Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)
* Prior treatment with ≥ 2 prior chemotherapy-based or immunotherapy-based regimens for iNHL
* Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
* Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL
* Lymphoma that is refractory to rituximab and to an alkylating agent
* Discontinuation of all other therapies for treatment of iNHL ≥ 3 weeks before Visit 2
* For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods
* Willingness and ability to provide written informed consent and to comply with the protocol requirements
Inclusion/
Gender
All
Gender Based
false
Keywords
indolent Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma
iNHL
NHL
GS-1101
CAL-101
PI3K
Phosphatidylinositol 3-kinase
Follicular Lymphoma (FL)
Small lymphocytic lymphoma (SLL)
Lymphoplasmacytoid lymphoma (LPL)
Marginal zone lymphoma (MZL)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01282424
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
101-09
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Study to Assess the Efficacy and Safety of Idelalisib in Subjects With Indolent B-Cell Non-Hodgkin Lymphomas Refractory to Rituximab and Alkylating Agents
Primary Outcomes
Outcome Description
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)
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)
Outcome Measure
Overall Response Rate
Outcome Time Frame
Start of Treatment to End of Treatment (up to 81 months)
Secondary Ids
Secondary Id
2010-022155-33
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Start of Treatment to End of Treatment (up to 81 months)
Outcome Measure
Duration of Response
Outcome Description
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.
Outcome Time Frame
Start of Treatment to End of Treatment (up to 81 months)
Outcome Measure
Lymph Node Response Rate
Outcome Description
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.
Outcome Time Frame
Start of Treatment to End of Treatment (up to 81 months)
Outcome Measure
Time to Response
Outcome Description
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.
Outcome Time Frame
Start of Treatment to End of Treatment (up to 81 months)
Outcome Measure
Progression-Free Survival
Outcome Description
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.
Outcome Time Frame
Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)
Outcome Measure
Overall Survival
Outcome Description
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.
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.
Outcome Time Frame
Baseline to End of Treatment (up to 81 months)
Outcome Measure
Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS)
Outcome Description
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.
Outcome Time Frame
Baseline to End of Treatment (up to 81 months)
Outcome Measure
Change in Karnofsky Performance Status
Outcome Description
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.
Outcome Time Frame
Enrollment to End of Treatment (up to 81 months)
Outcome Measure
Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines
Outcome Description
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.
Outcome Time Frame
Start of Treatment to End of Treatment (up to 81 months) plus 30 days
Outcome Measure
Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms
Outcome Description
The average idelalisib exposure was summarized.
Outcome Time Frame
Start of Treatment to End of Treatment (up to 81 months)
Outcome Measure
Study Drug Exposure
Outcome Time Frame
Predose and at 1.5 hours (± 5 minutes) postdose on Day 29
Outcome Measure
Idelalisib Plasma Concentration
Outcome Description
Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.
Outcome 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
Outcome Measure
PK Parameter: Cmax
Outcome Description
Tmax at Days 1 and 29 was analyzed. Tmax is defined as the time of Cmax (the maximum concentration of drug).
Outcome 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
Outcome Measure
PK Parameter: Tmax
Outcome Description
AUClast at Days 1 and 29 was analyzed. AUClast is defined as the concentration of drug from time zero to the last observable concentration
Outcome 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
Outcome Measure
PK Parameter: AUClast
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Noah Kornblum
Investigator Email
nkornblu@montefiore.org
Investigator Phone
718-920-4826