Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213)

A Phase 2, Multicenter, Open-Label Study of Parsaclisib, a PI3Kδ Inhibitor, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213)

The purpose of this study is to assess the efficacy and safety of parsaclisib in Japanese participants with relapsed or refractory follicular lymphoma

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: parsaclisib

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Anjo, Japan, 446-8602
    • Ja-Aichi Anjo Kosei Hospital
  • Fukui, Japan, 910-1193
    • University of Fukui Hospital
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Fukuoka, Japan, 806-8501
    • JCHO Kyushu Hospital
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Hirakata, Japan, 573-1191
    • Kansai Medical University Hospital
  • Hokkaido, Japan, 003-0006
    • Hokuyukai Sapporo Hokuyu Hospital
  • Hyogo, Japan, 663-8501
    • Hyogo College of Medicine Hospital
  • Ibaraki, Japan, 311-3193
    • NHO Mito Medical Center
  • Isehara, Japan, 259-1193
    • Tokai University Hospital
  • Kagoshima, Japan, 890-0064
    • Jiaikai Imamura General Hospital
  • Kobe, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Matsumoto, Japan, 399-8701
    • Nho Matsumoto Medical Center
  • Matsuyama, Japan, 791-0280
    • NHO Shikoku Cancer Center
  • Nagano, Japan, 380-8582
    • Nagano Red Cross Hospital
  • Nagoya, Japan, 466-8650
    • Japanese Red Cross Nagoya Daini Hospital
  • Nagoya, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Nagoya, Japan, 4668650
    • Red Cross Nagoya Daini Hospital
  • Nara, Japan, 632-8552
    • Tenri Hospital
  • Natori, Japan, 981-1293
    • Miyagi Cancer Center
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Ogaki, Japan, 5038502
    • Ogaki Municipal Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Sapporo, Japan, 003-0804
    • NHO Hokkaido Cancer Center
  • Sendai-shi, Japan, 980-8574
    • Tohoku University Hospital
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Yokohama, Japan, 232-0024
    • Yokohama City University Medical Center
  • Yokohama, Japan, 221-0855
    • Yokohama Municipal Citizens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female Japanese participant who must be ≥ 18 years of age
• Ability to comprehend and willingness to sign a written ICF and comply with all study visits and procedures
• Histologically confirmed, relapsed or refractory, FL Grade 1, 2, and 3a
• Ineligible for HSCT
• Must have been treated with at least 2 prior systemic therapies for FL
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the LD and ≥ 1.0 cm in the LPD, respectively) as assessed by CT or MRI
• Participants must be willing to undergo an incisional, excisional, or core needle lymph node or tissue biopsy or provide a lymph node or tissue biopsy collected after the completion of last therapy. An earlier archived lymph node or tissue biopsy is acceptable if hospitalization is required for biopsy (eg. no superficial lymph node) and SUVmax by FDG-PET is < 14
• ECOG performance status 0 to 2
• Life expectancy ≥ 12 weeks
• Adequate hematologic, hepatic, and renal functions ANC ≥ 1.0 × 109/L Hemoglobin ≥ 8.0 g/dL. Platelet count ≥ 50 × 109/L. Total bilirubin ≤ 1.5 × ULN. Participants with documented history of Gilbert's syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible.

ALT/AST ≤ 2.5× ULN or ≤ 5 × ULN in the presence of liver involvement. Calculated creatinine clearance ≥ 40 mL/min by the Cockcroft-Gault Equation or the estimated glomerular filtration rate ≥ 40 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula.

• Female participants agree to use medically acceptable contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test before the start of study drug administration.
• Female participants of childbearing potential must understand and accept that pregnancy must be avoided during participation in the study.
• Male participants should avoid fathering children from screening through at least 93 days after the last dose of study treatment.

Exclusion Criteria:

• Known histological transformation from indolent NHL to DLBCL
• History of central nervous system lymphoma (either primary or metastatic)

• Prior treatment with the following:

  1. Selective PI3Kδ or pan-PI3K inhibitors (eg, idelalisib, copanlisib, duvelisib, etc).
  2. Bruton's tyrosine kinase inhibitor (eg, ibrutinib).
• Allogeneic SCT within the last 6 months, or autologous SCT within the last 3 months before the date of study treatment administration
• Active graft-versus-host disease
• Use of immunosuppressive therapy within 28 days of the date of study treatment administration
• Concurrent anticancer therapy
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease
• Current or previous other malignancy within 3 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
• Hepatitis B (HBV) or HCV infection
• Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia

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: parsaclisib; parsaclisib will be taken orally QD with water without regard to food except on mornings of PK clinic visits	Drug: parsaclisib; parsaclisib will be taken orally QD with water without regard to food except on mornings of PK clinic visits; Other Names: INCB050465

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) as defined by revised response criteria for lymphoma, as determined by an Independent Review Committee (IRC). CR: target nodes/nodal masses regressed to ≤1.5 centimeters (cm) in the longest transverse diameter (LDi); no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate. PR: ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 target measurable nodes and extranodal sites; absent/regressed nonmeasured lesions (but no increase); spleen regressed by >50% in length beyond normal; and no new lesions.	up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR was defined as the time from the first documented evidence of CR or PR until disease progression or death from any cause among participants who achieved an objective response, as determined by radiographic disease assessment provided by an IRC. Progressive disease was defined as ≥1 of the following: abnormal individual node/lesion meeting specific criteria; new/recurrent splenomegaly; new/clear progression of pre-existing nonmeasured lesions; regrowth of any previously resolved lesions; new node >1.5 cm in any axis; new extranodal site >1.0 cm in any axis; assessable disease of any size attributable to lymphoma; new/recurrent involvement of bone marrow.	up to 20.0 months
Complete Response Rate (CRR)	CRR was defined as the percentage of participants with a CR as defined by revised response criteria for lymphoma, as determined by an IRC. CR was defined as: target nodes/nodal masses regressed to ≤1.5 cm in the LDi; no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate.	up to approximately 3 years
Progression-free Survival (PFS)	PFS was defined as the time from the date of the first dose of study treatment until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause. Progressive disease was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.	up to approximately 3 years
Overall Survival	Overall survival was defined as the time from the date of the first dose of study treatment until death from any cause.	up to approximately 3 years
Best Percentage Change in Target Lesion Size From Baseline, as Determined by Independent Review Committee and the Investigator	Target lesion size was measured by the sum of the products of the diameters of all target lesion sizes. The best percent change from Baseline was defined as the largest decrease, or smallest increase if no decrease, from Baseline in target lesion sizes on/before new anti-lymphoma therapy during the study. Percentage change was calculated as ([the post-Baseline value minus the Baseline value] / the Baseline value) x 100.	up to approximately 3 years
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug.	up to 1041 days
Number of Participants With Any Grade 3 or Higher TEAE	An adverse event was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.	up to 1041 days

Collaborators and Investigators

• Sponsor: Incyte Biosciences Japan GK
• Investigators: Study Director: Incyte Medical Monitor, Incyte Biosciences Japan GK

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): February 16, 2023
• Study Completion (Actual): October 13, 2023

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Follicular Lymphoma; Parsaclisib; PI3Kδ Inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular
• Other Study ID Numbers: INCB 50465-213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; 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
• product manufactured in and exported from the U.S.: Yes