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)

NCT ID: NCT02018861

Last Updated: 2023-09-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-22

Study Completion Date

2021-04-12

Brief Summary

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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.

Detailed Description

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Conditions

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B-Cell Malignancies

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Parsaclisib 5 mg QD

Parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Parsaclisib 10 mg QD

Parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Parsaclisib 15 mg QD

Parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Parsaclisib 20 mg QD

Parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Parsaclisib 30 mg QD

Parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Parsaclisib 45 mg QD

Parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Parsaclisib 20 mg + itacitinib (INCB039110) 300 mg

Parsaclisib 20 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Itacitinib

Intervention Type DRUG

Parsaclisib 30 mg + itacitinib (INCB039110) 300 mg

Parsaclisib 30 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

Itacitinib

Intervention Type DRUG

Parsaclisib 15 mg QD + R-ICE

Parsaclisib 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

Group Type PLACEBO_COMPARATOR

Parsaclisib

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Ifosfamide

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Parsaclisib 20 mg QD + R-ICE

20 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.

Group Type PLACEBO_COMPARATOR

Parsaclisib

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Ifosfamide

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Interventions

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Parsaclisib

Intervention Type DRUG

Itacitinib

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Ifosfamide

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Other Intervention Names

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INCB050465 INCB039110 itacitinib (INCB039110)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Claudia Corrado, M.D.

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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University of Alabama At Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Nyu Langone Laura and Isaac Perlmutter Cancer Center

New York, New York, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Greenville Health System Cancer Institute

Greenville, South Carolina, United States

Site Status

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 30803990 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Parsaclisib

Identifier Type: OTHER

Identifier Source: secondary_id

INCB 50465-101 (CITADEL-101)

Identifier Type: -

Identifier Source: org_study_id

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