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)

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

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).

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Indolent Non-Hodgkin Lymphoma; Lymphoplasmacytic Lymphoma (With or Without Waldenstrom Macroglobulinemia)
• Intervention / Treatment: Drug: Idelalisib

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
  • Miyagi, Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idelalisib; 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; 150 mg tablet(s) administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): December 25, 2014
• Study Completion (Actual): October 17, 2017

Study Registration Dates

• First Submitted: September 13, 2014
• First Submitted That Met QC Criteria: September 13, 2014
• First Posted (Estimate): September 16, 2014

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, B-Cell; Lymphoma; Lymphoma, B-Cell; Leukemia; Lymphoma, Non-Hodgkin; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Idelalisib
• Other Study ID Numbers: GS-US-313-1380

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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 Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No