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)

• ClinicalTrials.gov Identifier: NCT02018861
• Recruitment Status: Completed
• First Posted: December 23, 2013
• Results First Posted: June 28, 2022
• Last Update Posted: June 28, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: December 5, 2013
• First Posted Date: December 23, 2013
• Results First Submitted Date: April 7, 2022
• Results First Posted Date: June 28, 2022
• Last Update Posted Date: June 28, 2022
• Actual Study Start Date: September 22, 2016
• Actual Primary Completion Date: April 12, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 1, 2022)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 53 months (4.4 years) ]

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.

• Original Primary Outcome Measures (submitted: December 17, 2013): Safety and tolerability of INCB050465 as assessed by summary of clinical laboratory assessments, physical examination results, 12-lead ECGs, and summary of AEs. [ Time Frame: Measured every 3 weeks for approximately 15 months. ]

Current Secondary Outcome Measures (submitted: June 1, 2022)

• 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 [ Time Frame: Up to approximately 53 months (4.4 years) ]
  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.
• Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL [ Time Frame: Up to approximately 44 months (3.7 years) ]
  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.
• Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL [ Time Frame: Up to approximately 4 months ]
  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.
• Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM [ Time Frame: Up to approximately 53 months (4.4 years) ]
  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.
• Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM [ Time Frame: Up to approximately 44 months (3.7 years) ]
  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.
• Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM [ Time Frame: Up to approximately 4 months ]
  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.
• 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 [ Time Frame: Up to approximately 53 months (4.4 years) ]
  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.
• 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 [ Time Frame: Up to approximately 44 months (3.7 years) ]
  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.
• 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 [ Time Frame: Up to approximately 4 months ]
  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.
• Cmax of Itacitinib in Combination With Parsaclisib [ Time Frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  Cmax is defined as the maximum observed plasma or serum concentration of itacitinib.
• Tmax of Itacitinib in Combination With Parsaclisib [ Time Frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  tmax is defined as the time to the maximum concentration of itacitinib.
• Cmin of Itacitinib in Combination With Parsaclisib [ Time Frame: 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.
• AUC0-t of Itacitinib in Combination With Parsaclisib [ Time Frame: 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.
• AUC0-τ of Itacitinib in Combination With Parsaclisib [ Time Frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours [q12h] administration or from hour 0 to 24 for once every 24 hours [q24h] administration) of itacitinib.
• Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib [ Time Frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
• Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib [ Time Frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  tmax is defined as the time to the maximum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
• Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib [ Time Frame: Cycle 1 Days 1 and 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 parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
• Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib [ Time Frame: Cycle 1 Days 1 and 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 parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
• Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib [ Time Frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for q12h administration or from hour 0 to 24 for q24h administration) of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
• Part 3: Cmax of Parsaclisib Monotherapy [ Time Frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
• Part 3: Tmax of Parsaclisib Monotherapy [ Time Frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  tmax is defined as the time to the maximum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
• Part 3: Cmin of Parsaclisib Monotherapy [ Time Frame: Cycle 1 Days 1 and 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 parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
• Part 3: AUC0-t of Parsaclisib Monotherapy [ Time Frame: Cycle 1 Days 1 and 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 of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
• Part 3: AUC0-τ of Parsaclisib Monotherapy [ Time Frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose ]
  AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours [q12h] administration or from hour 0 to 24 for once every 24 hours [q24h] administration) of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.

Original Secondary Outcome Measures (submitted: December 17, 2013)

• Efficacy as measured by overall response defined as sum of subjects achieving a partial (PR) and a complete response (CR) of INCB050465 as monotherapy. [ Time Frame: Measured every 12 weeks for approximately 15 months. ]
  Overall response is based on:

  • International Working Group on Chronic Lymphocytic Leukemia (IWGCLL) criteria for CLL (Hallek et al 2008 and Cheson et al 2012).
  • Revised response criteria for lymphoma for Hodgkin's and non-Hodgkin's lymphoma (Cheson et al 2007 and Owen et al 2013)
• Pharmacokinetic collections to determine Cmax, Tmax, AUC0-t, AUC0-∞,T½, λz, CL/F, and Vz/F of INCB050465. [ Time Frame: Measured for each patient at Day 1 for up to 6 cycles (approximately 5 months). ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-Cell Malignancies

Intervention

• Drug: Parsaclisib
  Other Name: INCB050465
• Drug: Itacitinib
  Other Names:

  • INCB039110
  • itacitinib (INCB039110)
• Drug: Rituximab
• Drug: Ifosfamide
• Drug: Carboplatin
• Drug: Etoposide

Study Arms

• Experimental: Parsaclisib 5 mg QD
  Parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles
  Intervention: Drug: Parsaclisib
• Experimental: Parsaclisib 10 mg QD
  Parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles
  Intervention: Drug: Parsaclisib
• Experimental: Parsaclisib 15 mg QD
  Parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles
  Intervention: Drug: Parsaclisib
• Experimental: Parsaclisib 20 mg QD
  Parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles
  Intervention: Drug: Parsaclisib
• Experimental: Parsaclisib 30 mg QD
  Parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles
  Intervention: Drug: Parsaclisib
• Experimental: Parsaclisib 45 mg QD
  Parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles
  Intervention: Drug: Parsaclisib
• Experimental: 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
  Interventions:

  • Drug: Parsaclisib
  • Drug: Itacitinib
• Experimental: 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
  Interventions:

  • Drug: Parsaclisib
  • Drug: Itacitinib
• Placebo Comparator: 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
  Interventions:

  • Drug: Parsaclisib
  • Drug: Rituximab
  • Drug: Ifosfamide
  • Drug: Carboplatin
  • Drug: Etoposide
• Placebo Comparator: 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.
  Interventions:

  • Drug: Parsaclisib
  • Drug: Rituximab
  • Drug: Ifosfamide
  • Drug: Carboplatin
  • Drug: Etoposide

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 6, 2017): 88
• Original Estimated Enrollment (submitted: December 17, 2013): 40
• Actual Study Completion Date: April 12, 2021
• Actual Primary Completion Date: April 12, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02018861
• Other Study ID Numbers: INCB 50465-101 (CITADEL-101); Parsaclisib ( Other Identifier: Incyte Corporation )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Claudia Corrado, M.D.; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: June 2022