Clinical trial NCT02242045: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Indolent Non-Hodgkin Lymphoma
Follicular Lymphoma
Small Lymphocytic Lymphoma
Lymphoplasmacytic Lymphoma (With or Without Waldenstrom Macroglobulinemia)
Marginal Zone Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-09-16
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Within 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 28 days
measure: Percentage of Participants Experiencing TEAEs Related to Idelalisib Within 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 28 days
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Within 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
timeFrame: First dose date up to 28 days
measure: Percentage of Participants Who Permanently Discontinued Idelalisib Due to a TEAE Within 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 28 days
measure: Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 1
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1
measure: Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 8
timeFrame: Predose and 1.5 hours postdose on Day 8
measure: Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 15
timeFrame: Predose and 1.5 hours postdose on Day 15
measure: Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 22
timeFrame: Predose and 1.5 hours postdose on Day 22
measure: Plasma Concentration of Idelalisib and Its Major Metabolite GS-563117 on Day 29
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 29
Secondary outcomes:
measure: Percentage of Participants Experiencing TEAEs and SAEs Beyond 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 30 days after last dose (up to approximately 3 years)
measure: Percentage of Participants Experiencing TEAEs Related to Idelalisib Beyond 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 30 days after last dose (up to approximately 3 years)
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Beyond 28 Days of Idelalisib Exposure by Worst Grade at Postbaseline
timeFrame: First dose date up to 30 days after last dose (up to approximately 3 years)
measure: Percentage of Participants Who Permanently Discontinued Idelalisib Due to a TEAE Beyond 28 Days of Idelalisib Exposure
timeFrame: First dose date up to 30 days after last dose (up to approximately 3 years)
Other outcomes:
Locations:
city: Aichi
country: Japan
city: Miyagi
country: Japan
city: Tokyo
country: Japan
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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
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.