Back to resultsStudy 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)
Primary Purpose
Chronic Lymphocytic Leukemia, Indolent Non-Hodgkin Lymphoma, Follicular Lymphoma
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Idelalisib
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Idelalisib
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 8
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 15
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 22
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 29
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02242045
Brief Title
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)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
October 1, 2014 (Actual)
Primary Completion Date
December 25, 2014 (Actual)
Study Completion Date
October 17, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Indolent Non-Hodgkin Lymphoma, Follicular Lymphoma, Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma (With or Without Waldenstrom Macroglobulinemia), Marginal Zone Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Idelalisib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
Zydelig®, GS-1101, CAL-101
Intervention Description
150 mg tablet(s) administered orally twice daily
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Within 28 Days of Idelalisib Exposure
Description
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.
Time Frame
First dose date up to 28 days
Title
Percentage of Participants Experiencing TEAEs Related to Idelalisib Within 28 Days of Idelalisib Exposure
Description
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.
Time Frame
First dose date up to 28 days
Title
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Within 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
Description
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.
Time Frame
First dose date up to 28 days
Title
Percentage of Participants Who Permanently Discontinued Idelalisib Due to a TEAE Within 28 Days of Idelalisib Exposure
Description
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.
Time Frame
First dose date up to 28 days
Title
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 1
Description
Lower limit of quantitation was 5 ng/mL for idelalisib and metabolite GS-563117 both.
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1
Title
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 8
Time Frame
Predose and 1.5 hours postdose on Day 8
Title
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 15
Time Frame
Predose and 1.5 hours postdose on Day 15
Title
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 22
Time Frame
Predose and 1.5 hours postdose on Day 22
Title
Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 29
Time Frame
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 29
Secondary Outcome Measure Information:
Title
Percentage of Participants Experiencing TEAEs and SAEs Beyond 28 Days of Idelalisib Exposure
Description
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.
Time Frame
First dose date up to 30 days after last dose (up to approximately 3 years)
Title
Percentage of Participants Experiencing TEAEs Related to Idelalisib Beyond 28 Days of Idelalisib Exposure
Description
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.
Time Frame
First dose date up to 30 days after last dose (up to approximately 3 years)
Title
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Beyond 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
Description
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.
Time Frame
First dose date up to 30 days after last dose (up to approximately 3 years)
Title
Percentage of Participants Who Permanently Discontinued Idelalisib Due to a TEAE Beyond 28 Days of Idelalisib Exposure
Description
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.
Time Frame
First dose date up to 30 days after last dose (up to approximately 3 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Aichi
Country
Japan
City
Miyagi
Country
Japan
City
Tokyo
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency
Citations:
Citation
Kinoshita T, Fukuhara N, Nagai H, Izutsu K, Kobayashi Y, et al. Phase 1b and Pharmacokinetic Study of Idelalisib in Japanese Patients with Relapsed or Refractory (R/R) Indolent B-Cell Non-Hodgkin Lymphoma (iNHL) or Chronic Lymphocytic Leukemia (CLL) [Abstract 85914]. Blood 2015;126:5089
Results Reference
result
PubMed Identifier
32856068
Citation
Fukuhara N, Kinoshita T, Yamamoto K, Nagai H, Izutsu K, Yamamoto G, Bhargava P, Rajakumaraswamy N, Humeniuk R, Mathias A, Xing G, Fukui M, Tobinai K. Phase 1b study to investigate the safety and tolerability of idelalisib in Japanese patients with relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia. Jpn J Clin Oncol. 2020 Dec 16;50(12):1395-1402. doi: 10.1093/jjco/hyaa153.
Results Reference
result
Learn more about this trial
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)
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