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)

NCT02242045 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-313-1380
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

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).

Conditions

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

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (4)

• Percentage of Participants Experiencing TEAEs and SAEs Beyond 28 Days of Idelalisib Exposure

  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

  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

  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

  First dose date up to 30 days after last dose (up to approximately 3 years)

Study Arms (1)

Idelalisib

EXPERIMENTAL

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

Interventions

Idelalisib DRUG

150 mg tablet(s) administered orally twice daily

Also known as: Zydelig®, GS-1101, CAL-101

Idelalisib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (3)

Unknown Facility

Aichi, Japan

Location

Unknown Facility

Miyagi, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Related Publications (2)

• 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

  RESULT

• 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.

  PMID: 32856068 RESULT

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

idelalisib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 13, 2014
• First Posted: September 16, 2014
• Study Start: October 1, 2014
• Primary Completion: December 25, 2014
• Study Completion: October 17, 2017
• Last Updated: March 19, 2021
• Results First Posted: March 19, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

JP (3)