B-Cell MalignanciesPhase 1/2NCT02018861
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)
A Phase 1/2 study testing Parsaclisib, Itacitinib and Rituximab in people with B-Cell Malignancies, run by Incyte Corporation at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-Cell Malignancies
- What is being tested?
- Parsaclisib, Itacitinib and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 7 sitesUnited States
- Study dates
- 22 Sep 2016to 12 Apr 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years or older, with lymphoid malignancies of B-cell origin including:
- 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
- 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
Who cannot join
- 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 locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
University of Alabama At Birmingham Comprehensive Cancer Center
Birmingham, Alabama, 35205
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Karmanos Cancer Institute
Detroit, Michigan, 48201
Greenville Health System Cancer Institute
Greenville, South Carolina, 29605
Nyu Langone Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016
About this study
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)
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.
- Conditions
- B-Cell Malignancies
- Being tested
- Parsaclisib, Itacitinib, Rituximab, Ifosfamide, Carboplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParsaclisibDrug
Also called INCB050465
ItacitinibDrug
Also called INCB039110, itacitinib (INCB039110)
RituximabDrug
IfosfamideDrug
CarboplatinDrug
EtoposideDrug
| Study group | Role | What they receive |
|---|---|---|
| Parsaclisib 5 mg QD | Experimental | Parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles Receives: Drug: Parsaclisib |
| Parsaclisib 10 mg QD | Experimental | Parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles Receives: Drug: Parsaclisib |
| Parsaclisib 15 mg QD | Experimental | Parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles Receives: Drug: Parsaclisib |
| Parsaclisib 20 mg QD | Experimental | Parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles Receives: Drug: Parsaclisib |
| Parsaclisib 30 mg QD | Experimental | Parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles Receives: Drug: Parsaclisib |
| Parsaclisib 45 mg QD | Experimental | Parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles Receives: Drug: Parsaclisib |
| Parsaclisib 20 mg + itacitinib (INCB039110) 300 mg | Experimental | Parsaclisib 20 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles Receives: Drug: Parsaclisib; Drug: Itacitinib |
| Parsaclisib 30 mg + itacitinib (INCB039110) 300 mg | Experimental | Parsaclisib 30 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles Receives: Drug: Parsaclisib; Drug: Itacitinib |
| Parsaclisib 15 mg QD + R-ICE | Placebo comparator | 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 Receives: Drug: Parsaclisib; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide |
| Parsaclisib 20 mg QD + R-ICE | Placebo comparator | 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. Receives: Drug: Parsaclisib; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Measured: Up to approximately 53 months (4.4 years)
Secondary outcomes (24)
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
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.
Measured: Up to approximately 53 months (4.4 years)
Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
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.
Measured: Up to approximately 44 months (3.7 years)
Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
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.
Measured: Up to approximately 4 months
Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM
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.
Measured: Up to approximately 53 months (4.4 years)
Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
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.
Measured: Up to approximately 44 months (3.7 years)
Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
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.
Measured: Up to approximately 4 months
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
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.
Measured: Up to approximately 53 months (4.4 years)
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
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.
Measured: Up to approximately 44 months (3.7 years)
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
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.
Measured: Up to approximately 4 months
Cmax of Itacitinib in Combination With Parsaclisib
Cmax is defined as the maximum observed plasma or serum concentration of itacitinib.
Measured: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Tmax of Itacitinib in Combination With Parsaclisib
tmax is defined as the time to the maximum concentration of itacitinib.
Measured: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Cmin of Itacitinib in Combination With Parsaclisib
Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of itacitinib.
Measured: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
AUC0-t of Itacitinib in Combination With Parsaclisib
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.
Measured: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
AUC0-τ of Itacitinib in Combination With Parsaclisib
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.
Measured: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Part 3: Cmax of Parsaclisib Monotherapy
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Part 3: Tmax of Parsaclisib Monotherapy
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Part 3: Cmin of Parsaclisib Monotherapy
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Part 3: AUC0-t of Parsaclisib Monotherapy
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Part 3: AUC0-τ of Parsaclisib Monotherapy
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.
Measured: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2013 (estimated)
- Study start22 Sep 2016
- Primary completion12 Apr 2021
- Study completion12 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B-Cell MalignanciesStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Claudia Corrado, M.D., Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02018861
- Sponsor's protocol ID
- INCB 50465-101 (CITADEL-101)
- Other IDs
- Parsaclisib
- Status last verified
- Sep 2023
- First submitted
- 5 Dec 2013
- Last updated
- 28 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- Individual data sharing
- Undecided
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.
PubMed 30803990
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02018861
- Acronym / sponsor ID
- INCB 50465-101 (CITADEL-101)
- Conditions
- B-Cell Malignancies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- 22 Sep 2016 (actual)
- Primary completion
- 12 Apr 2021 (actual)
- Study completion
- 12 Apr 2021 (actual)
- First posted
- 23 Dec 2013 (estimated)
- Results
- Posted 28 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Parsaclisib 5 mg QD | Experimental | Drug: ParsaclisibParsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles |
| Parsaclisib 10 mg QD | Experimental | Drug: ParsaclisibParsaclisib 10 mg as oral tablets QD in 21-day treatment cycles |
| Parsaclisib 15 mg QD | Experimental | Drug: ParsaclisibParsaclisib 15 mg as oral tablets QD in 21-day treatment cycles |
| Parsaclisib 20 mg QD | Experimental | Drug: ParsaclisibParsaclisib 15 mg as oral tablets QD in 21-day treatment cycles |
| Parsaclisib 30 mg QD | Experimental | Drug: ParsaclisibParsaclisib 30 mg as oral tablets QD in 21-day treatment cycles |
| Parsaclisib 45 mg QD | Experimental | Drug: ParsaclisibParsaclisib 45 mg as oral tablets QD in 21-day treatment cycles |
| Parsaclisib 20 mg + itacitinib (INCB039110) 300 mg | Experimental | Drug: Parsaclisib, Drug: ItacitinibParsaclisib 20 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles |
| Parsaclisib 30 mg + itacitinib (INCB039110) 300 mg | Experimental | Drug: Parsaclisib, Drug: ItacitinibParsaclisib 30 mg as oral tablets QD and itacitinib (INCB039110) 300 mg as oral tablets QD in 21-day treatment cycles |
| Parsaclisib 15 mg QD + R-ICE | Placebo comparator | Drug: Parsaclisib, Drug: Rituximab, Drug: Ifosfamide, Drug: Carboplatin, Drug: EtoposideParsaclisib 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 | Placebo comparator | Drug: Parsaclisib, Drug: Rituximab, Drug: Ifosfamide, Drug: Carboplatin, Drug: Etoposide20 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Aged 18 years or older, with lymphoid malignancies of B-cell origin including:
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParsaclisibAlso: INCB050465 | Drug | Parsaclisib 10 mg QD, Parsaclisib 15 mg QD, Parsaclisib 15 mg QD + R-ICE, Parsaclisib 20 mg + itacitinib (INCB039110) 300 mg, Parsaclisib 20 mg QD, Parsaclisib 20 mg QD + R-ICE, Parsaclisib 30 mg + itacitinib (INCB039110) 300 mg, Parsaclisib 30 mg QD, Parsaclisib 45 mg QD, Parsaclisib 5 mg QD |
| ItacitinibAlso: INCB039110, itacitinib (INCB039110) | Drug | Parsaclisib 20 mg + itacitinib (INCB039110) 300 mg, Parsaclisib 30 mg + itacitinib (INCB039110) 300 mg |
| Rituximab | Drug | Parsaclisib 15 mg QD + R-ICE, Parsaclisib 20 mg QD + R-ICE |
| Ifosfamide | Drug | Parsaclisib 15 mg QD + R-ICE, Parsaclisib 20 mg QD + R-ICE |
| Carboplatin | Drug | Parsaclisib 15 mg QD + R-ICE, Parsaclisib 20 mg QD + R-ICE |
| Etoposide | Drug | Parsaclisib 15 mg QD + R-ICE, Parsaclisib 20 mg QD + R-ICE |
Primary outcome
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.
24 secondary outcomes
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)
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)
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
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)
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)
Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
Time frame: Up to approximately 4 months
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)
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)
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
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
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
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
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-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
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
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
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
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30803990Forero-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.
- Plain Language Summary of ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudia Corrado, M.D. study director
Incyte Corporation
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Parsaclisib, Itacitinib and Rituximab in people with B-Cell Malignancies, run by Incyte Corporation at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: Up to approximately 53 months (4.4 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02018861, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023; AzTrials last refreshed its copy on 31 Oct 2026.