B-cell Malignancies
Conditions
Brief summary
The study will be conducted in three parts. Part 1 is a dose escalation phase to determine the maximum tolerated dose (MTD) of INCB040093, a PI3Kδ inhibitor, or a tolerated, pharmacologically active dose; Part 2 will evaluate the combination of INCB040093 and itacitinib (INCB039110), a JAK1 inhibitor, to determine the MTD of the combination or a tolerated dose that produces substantial pharmacologic inhibition of both targets; Part 3 will further evaluate the chosen doses of INCB040093 alone and in combination with itacitinib (INCB039110) in subjects with relapsed/refractory B-cell malignancies.
Interventions
DRUGINCB040093
Escalating doses starting at 100 mg every day (QD)
DRUGINCB040093 + itacitinib
INCB040093 dose to be determined at completion of Part 1 of the study + itacitinib at a starting dose of 400 mg, QD with escalations planned up to 600 mg QD.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Aged 18 years or older, with lymphoid malignancies of B-cell origin as follows: \*Indolent / aggressive B-cell (NHL) Non- Hodgkin's Lymphoma: EXCLUDING: Burkitt lymphoma and precursor B-lymphoblastic leukemia/lymphoma INCLUDING: any non-Hodgkin's B-cell malignancy such as CLL and rare non-Hodgkin's B-cell subtypes such as Hairy Cell Leukemia, Waldenstrom macroglobulinemia, Mantle cell lymphoma, transformed NHL histologies, etc. \*Hodgkin's lymphoma * Life expectancy of 12 weeks or longer. * Subject must have received ≥ 1 prior treatment regimen. * The subject must not be a candidate for potentially curative therapy, including stem cell transplant.
Exclusion criteria
* Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study drug. * Received any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) prior to receiving their first dose of study drug (42 days for nitrosoureas) EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent). * Has any unresolved toxicity ≥ Grade 2 from previous anticancer therapy. * Has history of brain metastases or spinal cord compression, or lymphoma involving the central nervous system. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3. * Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or is currently receiving immunosuppressive therapy following allogeneic transplant. * Received autologous hematopoietic stem cell transplant within the last 3 months. * Laboratory parameters not within the protocol-defined range. * Current or recent history (\<30 days prior to screening and/or \<45 days prior to dosing) of a clinically meaningful bacterial, fungal, parasitic or mycobacterial infection. * Current clinically active viral infection. * Known history of infection with the human immunodeficiency virus (HIV). * History of active hepatitis or positive serology for hepatitis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of INCB040093 as monotherapy and when given in combination with itacitinib as determined by clinical laboratory assessments, physical exams, 12-lead ECG and summary of adverse events | Measured every 3 weeks until progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary efficacy as assessed by Overall Response Rate (ORR) as measured by published criteria for Hodgkin's/non-Hodgkin's lymphoma (Cheson et al 2007 and Owen et al 2013) and Chronic Lymphocytic Leukemia (CLL) (Cheson et el 2012) | Every 12 weeks (4 cycles) until study withdrawal | — |
| Pharmacokinetic (PK) collections. | Measured for each patient at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 1 Day 15 | Plasma concentrations of each INCB040093 and itacitinib will be used to estimate peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC). |
Countries
United States
Contacts
STUDY_DIRECTORPeter Langmuir, MD
Incyte Corporation
Outcome results
None listed