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))
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| ClinicalTrials.gov Identifier: NCT03235544 |
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Recruitment Status :
Active, not recruiting
First Posted : August 1, 2017
Results First Posted : February 10, 2022
Last Update Posted : November 18, 2023
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Sponsor:
Incyte Corporation
Information provided by (Responsible Party):
Incyte Corporation
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lymphoma | Drug: Parsaclisib | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 162 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | November 20, 2017 |
| Actual Primary Completion Date : | March 3, 2021 |
| Estimated Study Completion Date : | April 30, 2024 |
| Arm | Intervention/treatment |
|---|---|
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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. |
Drug: Parsaclisib
Parsaclisib tablets administered orally with water and without regard to food.
Other Name: INCB050465 |
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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. |
Drug: Parsaclisib
Parsaclisib tablets administered orally with water and without regard to food.
Other Name: INCB050465 |
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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. |
Drug: Parsaclisib
Parsaclisib tablets administered orally with water and without regard to food.
Other Name: INCB050465 |
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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. |
Drug: Parsaclisib
Parsaclisib tablets administered orally with water and without regard to food.
Other Name: INCB050465 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03235544
Locations
Show 103 study locations
Sponsors and Collaborators
Incyte Corporation
Investigators
| Study Director: | Fred Zheng, MD | Incyte Corporation |
Study Documents (Full-Text)
Documents provided by Incyte Corporation:
Documents provided by Incyte Corporation:
Study Protocol [PDF] January 30, 2020
Statistical Analysis Plan [PDF] January 28, 2021
| Responsible Party: | Incyte Corporation |
| ClinicalTrials.gov Identifier: | NCT03235544 |
| Other Study ID Numbers: |
INCB 50465-205 (CITADEL-205) Parsaclisib ( Other Identifier: Incyte Corporation ) 2017-003148-19 ( EudraCT Number ) |
| First Posted: | August 1, 2017 Key Record Dates |
| Results First Posted: | February 10, 2022 |
| Last Update Posted: | November 18, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (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 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Incyte Corporation:
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Mantle cell lymphoma non-Hodgkin lymphoma Bruton's tyrosine kinase (BTK) phosphatidylinositol 3-kinase (PI3K) |
Additional relevant MeSH terms:
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Lymphoma Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin |