Clinical trial NCT01905813: Study of INCB040093 in Subjects With Previously Treated B-Cell Malignancies
Official title: A Phase 1, Open-label, Dose Escalation, Safety and Tolerability Study of INCB040093 in Subjects With Previously Treated B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: B-cell Malignancies
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2013-07-23
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Measured every 3 weeks until progression.
Secondary outcomes:
measure: 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)
timeFrame: Every 12 weeks (4 cycles) until study withdrawal
measure: Pharmacokinetic (PK) collections.
timeFrame: Measured for each patient at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 1 Day 15
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Jacksonville
country: United States
state: Florida
city: Ann Arbor
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
Study officials:
affiliation: Incyte Corporation
name: Peter Langmuir, MD
role: STUDY_DIRECTOR
References:
citation: Phillips TJ, Forero-Torres A, Sher T, Diefenbach CS, Johnston P, Talpaz M, Pulini J, Zhou L, Scherle P, Chen X, Barr PM. Phase 1 study of the PI3Kdelta inhibitor INCB040093 +/- JAK1 inhibitor itacitinib in relapsed/refractory B-cell lymphoma. Blood. 2018 Jul 19;132(3):293-306. doi: 10.1182/blood-2017-10-812701. Epub 2018 Apr 25.