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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04434937
• Other study ID #: INCB 50465-213
• Status: Completed
• Phase: Phase 2
• Start date: September 30, 2020
• Est. completion date: October 13, 2023

Study information

• Verified date: December 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: October 13, 2023
• Est. primary completion date: February 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 PI3Kd 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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

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

Locations

Country	Name	City	State
Japan	Ja-Aichi Anjo Kosei Hospital	Anjo
Japan	University of Fukui Hospital	Fukui
Japan	Jcho Kyushu Hospital	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Kansai Medical University Hospital	Hirakata
Japan	Hokuyukai Sapporo Hokuyu Hospital	Hokkaido
Japan	Hyogo College of Medicine Hospital	Hyogo
Japan	Nho Mito Medical Center	Ibaraki
Japan	Tokai University Hospital	Isehara
Japan	Jiaikai Imamura General Hospital	Kagoshima
Japan	Kobe City Medical Center General Hospital	Kobe
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto
Japan	Nho Matsumoto Medical Center	Matsumoto
Japan	Nho Shikoku Cancer Center	Matsuyama
Japan	Nagano Red Cross Hospital	Nagano
Japan	Japanese Red Cross Nagoya Daini Hospital	Nagoya
Japan	National Hospital Organization Nagoya Medical Center	Nagoya
Japan	Red Cross Nagoya Daini Hospital	Nagoya
Japan	Tenri Hospital	Nara
Japan	Miyagi Cancer Center	Natori
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Ogaki Municipal Hospital	Ogaki
Japan	Okayama University Hospital	Okayama
Japan	Nho Hokkaido Cancer Center	Sapporo
Japan	Tohoku University Hospital	Sendai-shi
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Nippon Medical School Hospital	Tokyo
Japan	Yokohama City University Medical Center	Yokohama
Japan	Yokohama Municipal Citizens Hospital	Yokohama

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Biosciences Japan GK

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 28 months
Secondary	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 28 months
Secondary	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
Secondary	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 28 months
Secondary	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 28 months
Secondary	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 28 months
Secondary	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 833 days
Secondary	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 833 days