A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Itacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)
2 other identifiers
interventional
88
1 country
7
Brief Summary
Open-label, dose-escalation study in subjects with previously treated B-cell malignancies to find maximum tolerated dose (MTD) or pharmacologic active dose of a PI3Kδ inhibitor, parsaclisib, as monotherapy and in combination with: itacitinib (INCB039110), a JAK1 inhibitor; rituximab; and rituximab, ifosfamide, carboplatin, and etoposide. Parsaclisib inhibits PI3Kδ, a protein involved in growth and survival of B-cell cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2016
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 5, 2013
CompletedFirst Posted
Study publicly available on registry
December 23, 2013
CompletedStudy Start
First participant enrolled
September 22, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 12, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 12, 2021
CompletedResults Posted
Study results publicly available
June 28, 2022
CompletedSeptember 28, 2023
September 1, 2023
4.6 years
December 5, 2013
April 7, 2022
September 21, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. Abnormal laboratory values or test results occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, are considered clinically meaningful, require therapy (e.g., hematologic abnormality that requires transfusion), or require changes in the study drug(s). A TEAE is defined as an event that was reported for the first time, or the worsening of a pre-existing event, after the first dose of study drug.
Up to approximately 53 months (4.4 years)
Secondary Outcomes (24)
Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants
Up to approximately 53 months (4.4 years)
Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
Up to approximately 44 months (3.7 years)
Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
Up to approximately 4 months
Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM
Up to approximately 53 months (4.4 years)
Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
Up to approximately 44 months (3.7 years)
- +19 more secondary outcomes
Study Arms (10)
Parsaclisib 5 mg QD
EXPERIMENTALParsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles
Parsaclisib 10 mg QD
EXPERIMENTALParsaclisib 10 mg as oral tablets QD in 21-day treatment cycles
Parsaclisib 15 mg QD
EXPERIMENTALParsaclisib 15 mg as oral tablets QD in 21-day treatment cycles
Parsaclisib 20 mg QD
EXPERIMENTALParsaclisib 15 mg as oral tablets QD in 21-day treatment cycles
Parsaclisib 30 mg QD
EXPERIMENTALParsaclisib 30 mg as oral tablets QD in 21-day treatment cycles
Parsaclisib 45 mg QD
EXPERIMENTALParsaclisib 45 mg as oral tablets QD in 21-day treatment cycles
Parsaclisib 20 mg + itacitinib (INCB039110) 300 mg
EXPERIMENTALParsaclisib 20 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles
Parsaclisib 30 mg + itacitinib (INCB039110) 300 mg
EXPERIMENTALParsaclisib 30 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles
Parsaclisib 15 mg QD + R-ICE
PLACEBO COMPARATORParsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m\^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m\^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m\^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration
Parsaclisib 20 mg QD + R-ICE
PLACEBO COMPARATOR20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m\^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m\^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m\^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.
Interventions
Eligibility Criteria
You may qualify if:
- Aged 18 years or older, with lymphoid malignancies of B-cell origin including:
- Indolent / aggressive B-cell non-Hodgkin's lymphoma (NHL)
- EXCLUDING: Burkitt's lymphoma and precursor B lymphoblastic leukemia/lymphoma
- INCLUDING: any non-Hodgkin's B cell malignancy such as chronic lymphocytic leukemia (CLL) and rare non-Hodgkin's B- cell subtypes such as hairy cell leukemia, Waldenström macroglobulinemia (WM), mantle cell leukemia (MCL), and transformed NHL histologies
- Hodgkin's lymphoma (HL)
- Life expectancy of 12 weeks or longer
- Subject must have received ≥ 1 prior treatment regimen(s)
- The subject must not be a candidate for potentially curative therapy including hematopoietic stem cell transplantation, except where one of the standard therapy regimen combinations may be used prior to transplantation per standard medical practice
You may not qualify if:
- Has history of brain metastasis, spinal cord compression (unless treated, asymptomatic, and stable on most recent imaging and enrolling in expansion cohort), or lymphoma involving the central nervous system (CNS)
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3 (≥ 2 during dose escalation)
- Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or currently receiving immunosuppressive therapy following allogeneic transplant
- Received autologous hematopoietic stem cell transplant within the last 3 months
- Inadequate marrow reserve assessed by hematologic laboratory parameters
- Inadequate renal or liver function
- Known HIV infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
University of Alabama At Birmingham Comprehensive Cancer Center
Birmingham, Alabama, 35205, United States
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Nyu Langone Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016, United States
University Hospitals Case Medical Center
Cleveland, Ohio, 44106, United States
Greenville Health System Cancer Institute
Greenville, South Carolina, 29605, United States
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
Related Publications (1)
Forero-Torres A, Ramchandren R, Yacoub A, Wertheim MS, Edenfield WJ, Caimi P, Gutierrez M, Akard L, Escobar C, Call J, Persky D, Iyer S, DeMarini DJ, Zhou L, Chen X, Dawkins F, Phillips TJ. Parsaclisib, a potent and highly selective PI3Kdelta inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019 Apr 18;133(16):1742-1752. doi: 10.1182/blood-2018-08-867499. Epub 2019 Feb 25.
PMID: 30803990DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Incyte Corporation
Study Officials
- STUDY DIRECTOR
Claudia Corrado, M.D.
Incyte Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2013
First Posted
December 23, 2013
Study Start
September 22, 2016
Primary Completion
April 12, 2021
Study Completion
April 12, 2021
Last Updated
September 28, 2023
Results First Posted
June 28, 2022
Record last verified: 2023-09