Clinical trial NCT02018861: 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)
Official title: A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Iitacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: B-Cell Malignancies
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2013-12-23
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older, with lymphoid malignancies of B-cell origin including:

  1. 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
  2. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 53 months (4.4 years)
Secondary outcomes:
measure: 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
timeFrame: Up to approximately 53 months (4.4 years)
measure: Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
timeFrame: Up to approximately 44 months (3.7 years)
measure: Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
timeFrame: Up to approximately 4 months
measure: Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM
timeFrame: Up to approximately 53 months (4.4 years)
measure: Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
timeFrame: Up to approximately 44 months (3.7 years)
measure: Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
timeFrame: Up to approximately 4 months
measure: Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT
timeFrame: Up to approximately 53 months (4.4 years)
measure: Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT
timeFrame: Up to approximately 44 months (3.7 years)
measure: Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT
timeFrame: Up to approximately 4 months
measure: Cmax of Itacitinib in Combination With Parsaclisib
timeFrame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Tmax of Itacitinib in Combination With Parsaclisib
timeFrame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Cmin of Itacitinib in Combination With Parsaclisib
timeFrame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: AUC0-t of Itacitinib in Combination With Parsaclisib
timeFrame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: AUC0-τ of Itacitinib in Combination With Parsaclisib
timeFrame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Part 3: Cmax of Parsaclisib Monotherapy
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Part 3: Tmax of Parsaclisib Monotherapy
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Part 3: Cmin of Parsaclisib Monotherapy
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Part 3: AUC0-t of Parsaclisib Monotherapy
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Part 3: AUC0-τ of Parsaclisib Monotherapy
timeFrame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham Comprehensive Cancer Center
state: Alabama
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Nyu Langone Laura and Isaac Perlmutter Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute
state: South Carolina
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center
state: Texas
Study officials:
affiliation: Incyte Corporation
name: Claudia Corrado, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.