A Study of INCB050465 in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a Bruton's Tyrosine Kinase (BTK) Inhibitor ((CITADEL-205))

• ClinicalTrials.gov Identifier: NCT03235544
• Recruitment Status: Active, not recruiting
• First Posted: August 1, 2017
• Results First Posted: February 10, 2022
• Last Update Posted: November 18, 2023
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: July 27, 2017
• First Posted Date: August 1, 2017
• Results First Submitted Date: January 14, 2022
• Results First Posted Date: February 10, 2022
• Last Update Posted Date: November 18, 2023
• Actual Study Start Date: November 20, 2017
• Actual Primary Completion Date: March 3, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2022)

Objective Response Rate (ORR) [ Time Frame: Up to approximately 165 weeks ]

ORR=percentage of participants with complete response(CR) or partial response(PR) per revised response criteria for lymphomas,determined by independent review committee(IRC).Criteria for CR:1.Target nodes/nodal masses of lymph nodes,extralymphatic sites regressed to≤1.5cm in longest dimension transverse diameter of lesion(LDi);2.Absence of non-measured lesion;3.Organ enlargement regressed to normal;4.No new lesions;5.Normal bone marrow morphology;if indeterminate,immunohistochemistry negative.Criteria for PR:1.Lymph nodes,extralymphatic sites- ≥50%decrease in sum of product of perpendicular diameters for multiple lesions(SPD)of up to 6 target measurable nodes,extranodal sites;if lesion is too small to measure on computed tomography(CT),assign5mm×5mm as default;if no longer visible,0×0mm.Node>5mm×5mm but smaller than normal,use actual measurement.2.Absent/regressed non-measured lesions,no increase.3.Organ enlargement-Spleen regressed by>50%in length beyond normal.4.No new lesions.

Original Primary Outcome Measures (submitted: July 27, 2017)

Objective response rate [ Time Frame: Protocol-defined timepoints throughout the treatment period, up to approximately 16 months per participant. ]

Defined as the percentage of participants with a complete response (CR) or partial response (PR) as determined by computed tomography (CT)-based response criteria for lymphomas.

Current Secondary Outcome Measures (submitted: January 14, 2022)

• Duration of Response (DOR) [ Time Frame: Up to approximately 165 weeks ]
  DOR=time from first documented evidence of CR or PR until disease progression or death from any cause among participants who achieve an objective response as determined by IRC. Criteria for CR: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative. The criteria for PR included: 1.Lymph nodes and extralymphatic sites- a. ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; b. when a lesion is too small to measure on CT, assign 5 mm×5 mm as the default; c.when no longer visible, 0×0 mm. For a node >5 mm×5 mm but smaller than normal, use actual measurement. 2.Non-measured lesions- Absent/regressed, but no increase. 3. Organ enlargement-Spleen must have regressed by >50% in length beyond normal. 4.No new lesions.
• Complete Response Rate (CRR) [ Time Frame: Up to approximately 165 weeks ]
  CRR is defined as the percentage of participants with a CR as defined by response criteria for lymphomas, as determined by an IRC. The criteria for CR included: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative.
• Progression-Free Survival (PFS) [ Time Frame: Up to approximately 165 weeks ]
  PFS is 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.
• Overall Survival (OS) [ Time Frame: Up to approximately 165 weeks ]
  OS is defined as the time from the date of the first dose of study treatment until death from any cause.
• Best Percent Change From Baseline in Target Lesion Size [ Time Frame: Up to approximately 165 weeks ]
  Target lesion size is measured by the sum of the product of diameters of all target lesion sizes and is determined by the IRC. The best percent change from Baseline is defined as the largest decrease, or smallest increase if no decrease available, from Baseline in target lesion sizes on/before new (next-line) anti-lymphoma therapy during the study. Baseline is the last nonmissing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement.
• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study drug up to approximately 165 weeks ]
  An adverse event (AE) is any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug regardless of starting new anti-lymphoma therapy. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention.

Original Secondary Outcome Measures (submitted: July 27, 2017)

• Duration of response [ Time Frame: Protocol-defined timepoints throughout the treatment period, up to approximately 16 months per participant. ]
  Defined as the time from first documented evidence of CR or PR until disease progression or death from any cause among subjects who achieve an objective response.
• Complete response rate [ Time Frame: Protocol-defined timepoints throughout the treatment period, up to approximately 16 months per participant. ]
  Defined as the percentage of participants with a CR as defined by response criteria for lymphomas.
• Progression-free survival [ Time Frame: Protocol-defined timepoints throughout the treatment period, up to approximately 16 months per participant. ]
  Defined as the time from the date of the first dose of study treatment until the earliest date of disease progression or death from any cause.
• Overall survival [ Time Frame: Protocol-defined timepoints throughout the treatment period, up to approximately 26 months. ]
  Defined as the time from the date of the first dose of study treatment until death from any cause.
• Best percentage change in target lesion size from baseline [ Time Frame: Protocol-defined timepoints throughout the treatment period, up to approximately 16 months per participant. ]
  Target lesion size measured by the sum of the product of diameters of all target lesion sizes.
• Safety and tolerability of INCB050465 as measured by adverse events (AEs) [ Time Frame: Up to approximately 16 months per participant. ]
  An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a subject provides informed consent.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of INCB050465 in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a Bruton's Tyrosine Kinase (BTK) Inhibitor
• Official Title: A Phase 2, Open-Label, 2-Cohort, Multicenter Study of INCB050465, a PI3Kδ Inhibitor, in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a BTK Inhibitor (CITADEL-205)
• Brief Summary: This is a Phase 2, open-label, 2-cohort study designed to evaluate the efficacy and safety of 2 parsaclisib treatment regimens in participants with relapsed or refractory mantle cell lymphoma (MCL) previously treated either with or without a Bruton's tyrosine kinase (BTK) inhibitor.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

Drug: Parsaclisib

Parsaclisib tablets administered orally with water and without regard to food.

Other Name: INCB050465

Study Arms

• Experimental: Cohort 1: Treatment A (Exposed to Ibrutinib)

  Participants received parsaclisib 20 mg tablets, orally, once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to 52 weeks.

  Participants who were exposed to ibrutinib before enrollment were included in this group.

  Intervention: Drug: Parsaclisib
• Experimental: Cohort 1: Treatment B (Exposed to Ibrutinib)

  Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 2.5 mg QD for up to 116 weeks.

  Participants who were exposed to ibrutinib before enrollment were included in this group.

  Intervention: Drug: Parsaclisib
• Experimental: Cohort 2: Treatment A (Bruton's Tyrosine Kinase Inhibitor Naïve)

  Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 20 mg QW for up to approximately 145 weeks.

  Participants who had not received a BTK inhibitor previously were included in this group.

  Intervention: Drug: Parsaclisib
• Experimental: Cohort 2: Treatment B (Bruton's Tyrosine Kinase Inhibitor Naïve)

  Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 2.5 mg QD for up to approximately 136 weeks.

  Participants who had not received a BTK inhibitor previously were included in this group.

  Intervention: Drug: Parsaclisib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 16, 2023): 162
• Original Estimated Enrollment (submitted: July 27, 2017): 120
• Estimated Study Completion Date: April 30, 2024
• Actual Primary Completion Date: March 3, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men and women, aged 18 years or older.
• Documented failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen.
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

Exclusion Criteria:

• History of central nervous system lymphoma (either primary or metastatic).
• Prior treatment with idelalisib, other selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors, or a pan PI3K inhibitor.
• Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of first dose of study treatment.
• Active graft-versus-host disease.
• Liver disease: Participants positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for hepatitis B virus-deoxyribonucleic acid (HBV-DNA). Participants positive for anti-hepatitis C virus (HCV) antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, Denmark, France, Germany, Israel, Italy, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03235544
• Other Study ID Numbers: INCB 50465-205 (CITADEL-205); Parsaclisib ( Other Identifier: Incyte Corporation ); 2017-003148-19 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data (IPD) will be made available to interested researchers after the end of study, a thorough analysis, and the publication of the data in the clinical study report (CSR). As required, results of the data will be posted to ClinicalTrials.gov. Upon request, individual investigators may obtain IPD from the sponsor. The format for data delivery will be determined between sponsor and investigator.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• 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.
• URL: https://www.incyte.com/our-company/compliance-and-transparency

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Fred Zheng, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: November 2023