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)

Incyte

Status and phase: Completed; Phase 2; Phase 1

Conditions: B-Cell Malignancies

Treatments: Drug: Carboplatin; Drug: Parsaclisib; Drug: Etoposide; Drug: Rituximab; Drug: Ifosfamide; Drug: Itacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02018861

INCB 50465-101 (CITADEL-101)

Parsaclisib (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 88 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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88 participants in 10 patient groups, including a placebo group

Parsaclisib 5 mg QD

Experimental group

Description:

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

Treatment:

Drug: Parsaclisib

Parsaclisib 10 mg QD

Experimental group

Description:

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

Treatment:

Drug: Parsaclisib

Parsaclisib 15 mg QD

Experimental group

Description:

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

Treatment:

Drug: Parsaclisib

Parsaclisib 20 mg QD

Experimental group

Description:

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

Treatment:

Drug: Parsaclisib

Parsaclisib 30 mg QD

Experimental group

Description:

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

Treatment:

Drug: Parsaclisib

Parsaclisib 45 mg QD

Experimental group

Description:

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

Treatment:

Drug: Parsaclisib

Parsaclisib 20 mg + itacitinib (INCB039110) 300 mg

Experimental group

Description:

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

Treatment:

Drug: Itacitinib

Drug: Parsaclisib

Parsaclisib 30 mg + itacitinib (INCB039110) 300 mg

Experimental group

Description:

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

Treatment:

Drug: Itacitinib

Drug: Parsaclisib

Parsaclisib 15 mg QD + R-ICE

Placebo Comparator group

Description:

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

Treatment:

Drug: Ifosfamide

Drug: Rituximab

Drug: Etoposide

Drug: Parsaclisib

Drug: Carboplatin

Parsaclisib 20 mg QD + R-ICE

Placebo Comparator group

Description:

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.

Treatment:

Drug: Ifosfamide

Drug: Rituximab

Drug: Etoposide

Drug: Parsaclisib

Drug: Carboplatin