Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Idelalisib in Japanese Participants With Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphomas (iNHL) or Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the 28-day safety and tolerability, and to determine the pharmacokinetics (PK) of idelalisib in Japanese participants with relapsed or refractory indolent B-cell non-Hodgkin lymphomas (iNHL) or chronic lymphocytic leukemia (CLL).

Official Title
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A Phase 1b Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Idelalisib in Japanese Subjects With Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphomas or Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia, Indolent Non-Hodgkin Lymphoma, Follicular Lymphoma, Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma (With or Without Waldenstrom Macroglobulinemia), Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: Idelalisib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants with mature B-cell malignancies of iNHL including follicular lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, and CLL by World Health Organization classification Must have been born in Japan and must not have lived outside of Japan for > 1 year in the 5 years prior to Day 1 Must be able to trace maternal and paternal ancestry of parents and grandparents as Japanese Must have been previously treated with at least 1 regimen for iNHL or CLL and currently require treatment Discontinuation of all therapy (including radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of iNHL or CLL ≥ 4 weeks prior to Day 1 Eastern Cooperative Oncology Group performance status of 0 or 1 Required baseline laboratory data (within 4 weeks prior to Day 1) A negative serum pregnancy test for female participants of childbearing potential Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the individual's disease. Key Exclusion Criteria: Known histological transformation to an aggressive histology Known presence of myelodysplastic syndrome History of iNHL or CLL with central nervous system involvement Life expectancy < 120 days as per investigator assessment History of a nonlymphoid malignancy with the following exceptions: the malignancy has been in remission without treatment for ≥ 5 years prior to Day 1, or carcinoma in situ of the cervix, or adequately treated basal or squamous cell skin cancer or other localized nonmelanoma skin cancer, or surgically treated low-grade prostate cancer, or ductal carcinoma in situ of the breast treated with lumpectomy alone On-going drug-induced liver injury, alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension History or diagnosis of pneumonitis or interstitial lung disease. On-going inflammatory bowel disease Pregnancy or breastfeeding History of prior allogeneic hematopoietic stem cell or solid organ transplantation Concurrent participation in another therapeutic clinical trial Prior or on-going clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram finding, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the individual or impair the assessment of study results. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idelalisib<br>Participants with iNHL or CLL will receive idelalisib until the earliest of the following: unacceptable toxicity, substantial noncompliance, disease progression, pregnancy, initiation of another anticancer or experimental therapy, investigator discretion, or idelalisib discontinuation. | Drug: Idelalisib<br>* 150 mg tablet(s) administered orally twice daily<br>* Other names: CAL-101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Within 28 Days of Idelalisib Exposure | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug. | First dose date up to 28 days | 
| Percentage of Participants Experiencing TEAEs Related to Idelalisib Within 28 Days of Idelalisib Exposure | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug. | First dose date up to 28 days | 
| Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Within 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline | Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. If the relevant baseline laboratory value was missing, then any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment-emergent.The most severe graded abnormality from all tests was counted for each participant. Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. | First dose date up to 28 days | 
| Percentage of Participants Who Permanently Discontinued Idelalisib Due to a TEAE Within 28 Days of Idelalisib Exposure | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug. | First dose date up to 28 days | 
| Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 1 | Lower limit of quantitation was 5 ng/mL for idelalisib and metabolite GS-563117 both. | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 | 
| Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 8 |  | Predose and 1.5 hours postdose on Day 8 | 
| Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 15 |  | Predose and 1.5 hours postdose on Day 15 | 
| Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 22 |  | Predose and 1.5 hours postdose on Day 22 | 
| Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 29 |  | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing TEAEs and SAEs Beyond 28 Days of Idelalisib Exposure | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug. | First dose date up to 30 days after last dose (up to approximately 3 years) | 
| Percentage of Participants Experiencing TEAEs Related to Idelalisib Beyond 28 Days of Idelalisib Exposure | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug. | First dose date up to 30 days after last dose (up to approximately 3 years) | 
| Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Beyond 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline | Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Treatment-emergent laboratory abnormalities were graded per CTCAE, Version 4.03 where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. | First dose date up to 30 days after last dose (up to approximately 3 years) | 
| Percentage of Participants Who Permanently Discontinued Idelalisib Due to a TEAE Beyond 28 Days of Idelalisib Exposure | An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug. | First dose date up to 30 days after last dose (up to approximately 3 years) |