Trial Outcomes & Findings for 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 NCT02018861)

NCT ID: NCT02018861

Last Updated: 2023-09-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

88 participants

Primary outcome timeframe

Up to approximately 53 months (4.4 years)

Results posted on

2023-09-28

Participant Flow

This study was conducted at 13 study centers in the United States.

This was a 4-part study. Part 1 parsaclisib monotherapy dose escalation determined the recommended dose(s) (RDs) to explore. Part 2 evaluated the combination of parsaclisib and itacitinib to determine the RDs. Part 3 expansion further evaluated the RDs of parsaclisib as monotherapy and in combination with itacitinib in disease cohorts. Part 6 consisted of a safety assessment of parsaclisib in combination with the chemotherapy regimen R-ICE (rituximab, ifosfamide, carboplatin, and etoposide).

Participant milestones

Participant milestones
Measure	Parsaclisib 5 mg QD Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
Parsaclisib Monotherapy: 21-day Cycles STARTED	1	3	3	34	27	4	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles COMPLETED	0	0	0	4	0	0	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles NOT COMPLETED	1	3	3	30	27	4	0	0	0	0
Parsaclisib + Itacitinib; 21-day Cycles STARTED	0	0	0	0	0	0	8	3	0	0
Parsaclisib + Itacitinib; 21-day Cycles COMPLETED	0	0	0	0	0	0	0	0	0	0
Parsaclisib + Itacitinib; 21-day Cycles NOT COMPLETED	0	0	0	0	0	0	8	3	0	0
Parsaclisib + R-ICE; 21-day Cycles STARTED	0	0	0	0	0	0	0	0	4	1
Parsaclisib + R-ICE; 21-day Cycles COMPLETED	0	0	0	0	0	0	0	0	1	1
Parsaclisib + R-ICE; 21-day Cycles NOT COMPLETED	0	0	0	0	0	0	0	0	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Parsaclisib 5 mg QD Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.
Parsaclisib Monotherapy: 21-day Cycles Adverse Event	0	2	1	6	4	1	0	0	0
Parsaclisib Monotherapy: 21-day Cycles Withdrawal by Subject	0	0	0	1	1	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles Disease Progression	0	1	1	13	18	1	0	0	0
Parsaclisib Monotherapy: 21-day Cycles Death	1	0	0	3	1	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles Lost to Follow-up	0	0	1	1	0	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles Non-compliance with Study Treatment	0	0	0	0	1	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles Physician Decision	0	0	0	4	1	2	0	0	0
Parsaclisib Monotherapy: 21-day Cycles Unknown or Not Reported	0	0	0	2	1	0	0	0	0
Parsaclisib + Itacitinib; 21-day Cycles Disease Progression	0	0	0	0	0	0	5	2	0
Parsaclisib + Itacitinib; 21-day Cycles Unknown or Not Reported	0	0	0	0	0	0	3	1	0
Parsaclisib + R-ICE; 21-day Cycles Physician Decision	0	0	0	0	0	0	0	0	1
Parsaclisib + R-ICE; 21-day Cycles Disease Progression	0	0	0	0	0	0	0	0	1
Parsaclisib + R-ICE; 21-day Cycles Adverse Event	0	0	0	0	0	0	0	0	1

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parsaclisib 5 mg QD n=1 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD n=3 Participants Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD n=3 Participants Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD n=34 Participants Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD n=27 Participants Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD n=4 Participants Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg n=8 Participants Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg n=3 Participants Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE n=4 Participants Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE n=1 Participants Participants self-administered parsaclisib 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.	Total n=88 Participants Total of all reporting groups
Age, Continuous	NA years STANDARD_DEVIATION NA • n=5 Participants	69.0 years STANDARD_DEVIATION 16.52 • n=7 Participants	63.3 years STANDARD_DEVIATION 9.45 • n=5 Participants	62.4 years STANDARD_DEVIATION 16.48 • n=4 Participants	63.7 years STANDARD_DEVIATION 11.81 • n=21 Participants	66.8 years STANDARD_DEVIATION 8.77 • n=8 Participants	64.6 years STANDARD_DEVIATION 17.15 • n=8 Participants	51.7 years STANDARD_DEVIATION 27.02 • n=24 Participants	62.3 years STANDARD_DEVIATION 8.26 • n=42 Participants	NA years STANDARD_DEVIATION NA • n=42 Participants	63.3 years STANDARD_DEVIATION 14.44 • n=42 Participants
Sex/Gender, Customized Female	NA participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants	12 participants n=4 Participants	14 participants n=21 Participants	NA participants n=8 Participants	NA participants n=8 Participants	NA participants n=24 Participants	NA participants n=42 Participants	NA participants n=42 Participants	38 participants n=42 Participants
Sex/Gender, Customized Male	NA participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants	22 participants n=4 Participants	13 participants n=21 Participants	NA participants n=8 Participants	NA participants n=8 Participants	NA participants n=24 Participants	NA participants n=42 Participants	NA participants n=42 Participants	50 participants n=42 Participants
Race/Ethnicity, Customized Black or African American	NA participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants	4 participants n=4 Participants	4 participants n=21 Participants	NA participants n=8 Participants	NA participants n=8 Participants	NA participants n=24 Participants	NA participants n=42 Participants	NA participants n=42 Participants	9 participants n=42 Participants
Race/Ethnicity, Customized White	NA participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants	25 participants n=4 Participants	21 participants n=21 Participants	NA participants n=8 Participants	NA participants n=8 Participants	NA participants n=24 Participants	NA participants n=42 Participants	NA participants n=42 Participants	70 participants n=42 Participants
Race/Ethnicity, Customized Unknown or Not Reported	NA participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants	5 participants n=4 Participants	2 participants n=21 Participants	NA participants n=8 Participants	NA participants n=8 Participants	NA participants n=24 Participants	NA participants n=42 Participants	NA participants n=42 Participants	9 participants n=42 Participants

PRIMARY outcome

Timeframe: Up to approximately 53 months (4.4 years)

Population: Safety Population: all participants enrolled in the study who received at least 1 dose of parsaclisib, itacitinib, rituximab, ifosfamide, carboplatin, and/or etoposide

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=1 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD n=3 Participants Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD n=3 Participants Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD n=34 Participants Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD n=27 Participants Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD n=4 Participants Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg n=8 Participants Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg n=3 Participants Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE n=4 Participants Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE n=1 Participants Participants self-administered parsaclisib 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	1 Participants	3 Participants	3 Participants	32 Participants	25 Participants	4 Participants	6 Participants	3 Participants	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to approximately 53 months (4.4 years)

Population: Intent-to-Treat (ITT) Population: all participants with CLL enrolled in the study who received at least 1 dose of parsaclisib, itacitinib, rituximab, ifosfamide, carboplatin, and/or etoposide. Confidence intervals were calculated based on the exact method for binomial distributions.

CR: (a) peripheral blood lymphocytes \<4 x 10\^9/Liter (L); (b) no significant lymphadenopathy and lymph nodes \<1.5 centimeters (cm) in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10\^9/L; (f) platelets ≥100 x 10\^9/L; (g) hemoglobin ≥11.0 grams/deciliter (g/dL) (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10\^9/L or increase ≥50% over Baseline; (b) hemoglobin ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD n=1 Participants Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD n=1 Participants Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD n=3 Participants Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD n=1 Participants Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
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	—	0.0 percentage of participants Interval 0.0 to 97.5	—	0.0 percentage of participants Interval 0.0 to 97.5	66.7 percentage of participants Interval 9.4 to 99.2	0.0 percentage of participants Interval 0.0 to 97.5	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 44 months (3.7 years)

Population: ITT Population: all participants with CLL. Confidence intervals were calculated based on the exact method for binomial distributions.

CR: (a) peripheral blood lymphocytes \<4 x 10\^9/L; (b) no significant lymphadenopathy and lymph nodes \<1.5 cm in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10\^9/L; (f) platelets ≥100 x 10\^9/L; (g) hemoglobin ≥11.0 g/dL (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10\^9/L or increase ≥50% over Baseline; (b) ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=1 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL	100.0 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 4 months

Population: ITT Population: all participants with CLL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 53 months (4.4 years)

Population: ITT Population: all participants with WM. Confidence intervals were calculated based on the exact method for binomial distributions.

ORR: sum of participants achieving minor response (MR), PR, very good partial response (VGPR), and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at Baseline (BL); (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but \<90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but \<50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD n=1 Participants Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM	—	—	—	100.0 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 44 months (3.7 years)

Population: ITT Population: all participants with WM. Confidence intervals were calculated based on the exact method for binomial distributions.

ORR: sum of participants achieving MR, PR, VGPR, and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but \<90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but \<50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 4 months

Population: ITT Population: all participants with WM

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 53 months (4.4 years)

Population: ITT Population: all participants with the indicated types of HL and NHL. Confidence intervals were calculated based on the exact method for binomial distributions.

CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by \> 50% in length beyond normal; (c) NNLs.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=1 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD n=2 Participants Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD n=3 Participants Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD n=32 Participants Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD n=24 Participants Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD n=3 Participants Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
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 Marginal zone lymphoma	—	—	—	—	0.0 percentage of participants Interval 0.0 to 97.5	—	—	—	—	—
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 Diffuse large B-cell lymphoma	0.0 percentage of participants Interval 0.0 to 97.5	0.0 percentage of participants Interval 0.0 to 97.5	50.0 percentage of participants Interval 1.3 to 98.7	36.4 percentage of participants Interval 10.9 to 69.2	16.7 percentage of participants Interval 0.4 to 64.1	50.0 percentage of participants Interval 1.3 to 98.7	—	—	—	—
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 Follicular lymphoma	—	100.0 percentage of participants Interval 2.5 to 100.0	100.0 percentage of participants Interval 2.5 to 100.0	85.7 percentage of participants Interval 42.1 to 99.6	40.0 percentage of participants Interval 5.3 to 85.3	—	—	—	—	—
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 Mantle cell lymphoma	—	—	—	66.7 percentage of participants Interval 22.3 to 95.7	100.0 percentage of participants Interval 15.8 to 100.0	0.0 percentage of participants Interval 0.0 to 97.5	—	—	—	—
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 Extranodal marginal zone lymphoma of mucosa-associated lymphatic tissue	—	—	—	50.0 percentage of participants Interval 1.3 to 98.7	—	—	—	—	—	—
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 Nodal marginal zone B-cell lymphoma	—	—	—	100.0 percentage of participants Interval 2.5 to 100.0	100.0 percentage of participants Interval 29.2 to 100.0	—	—	—	—	—
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 Splenic marginal zone lymphoma	—	—	—	100.0 percentage of participants Interval 2.5 to 100.0	100.0 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—
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 Classical Hodgkin's lymphoma	—	—	—	50.0 percentage of participants Interval 6.8 to 93.2	0.0 percentage of participants Interval 0.0 to 52.2	—	—	—	—	—
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 Nodular lymphocytic-predominant Hodgkin's lymphoma	—	—	—	—	0.0 percentage of participants Interval 0.0 to 97.5	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 44 months (3.7 years)

Population: ITT Population: all participants with the indicated types of HL and NHL. Confidence intervals were calculated based on the exact method for binomial distributions.

CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by \> 50% in length beyond normal; (c) NNLs.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=7 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD n=3 Participants Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
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 Diffuse large B-cell lymphoma	0.0 percentage of participants Interval 0.0 to 70.8	0.0 percentage of participants Interval 0.0 to 70.8	—	—	—	—	—	—	—	—
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 Follicular lymphoma	0.0 percentage of participants Interval 0.0 to 97.5	—	—	—	—	—	—	—	—	—
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 Mantle cell lymphoma	100.0 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—	—	—	—
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 Classical Hodgkin's lymphoma	50.0 percentage of participants Interval 1.3 to 98.7	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 4 months

Population: ITT Population: all participants with the indicated types of HL and NHL

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=4 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD n=1 Participants Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
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 Diffuse large B-cell lymphoma	50.0 percentage of participants Summary statistics are not available due to the small sample size in Part 6.	100.0 percentage of participants Summary statistics are not available due to the small sample size in Part 6.	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: Pharmacokinetic (PK)/Pharmacodynamics (PD) Population: participants in the ITT/Safety Population who had PK/PD data. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Cmax is defined as the maximum observed plasma or serum concentration of itacitinib.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=7 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
Cmax of Itacitinib in Combination With Parsaclisib	887 nanomoles (nmol) Standard Deviation 404	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

tmax is defined as the time to the maximum concentration of itacitinib.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=7 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
Tmax of Itacitinib in Combination With Parsaclisib	2.0 hours Interval 1.0 to 4.0	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of itacitinib.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=7 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
Cmin of Itacitinib in Combination With Parsaclisib	32.8 nmol Standard Deviation 32.5	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of itacitinib.

Outcome measures

Outcome measures
Measure	Parsaclisib 5 mg QD n=7 Participants Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Parsaclisib 15 mg QD + R-ICE Participants self-administered 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.	Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 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.
AUC0-t of Itacitinib in Combination With Parsaclisib	6450 hours (hr)*nmol/L Standard Deviation 3780	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose