Clinical trial NCT02760485: A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Official title: An Open-Label Phase 1/2 Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: Diffuse large B-cell lymphoma
Relapsed Diffuse large B-cell lymphoma
Refractory Diffuse large B-cell lymphoma
activated B cell
germinal center B-cell
non-Hodgkin lymphoma
JAK1 inhibitor
Bruton's tyrosine kinase (BTK) inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2016-05-03
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety/tolerability and efficacy of itacitinib in combination with ibrutinib in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)


Eligibility criteria: Inclusion Criteria:

* Histologically documented diagnosis of DLBCL.

  * Phase 1: any DLBCL subtype.
  * Phase 2: activated B-cell or unclassifiable subtypes confirmed by immunohistochemistry using the Hans algorithm
* Relapsed or refractory DLBCL, defined as having received at least 1 but no more than 3 prior treatment regimens and ineligible for high-dose chemotherapy/autologous stem cell transplant.
* Fluorodeoxyglucose-avid disease (based on local evaluation) per the Lugano Classification. Fluorodeoxyglucose-avid disease is defined as disease with a 5-point scale score of 4 or 5.
* Archived tumor tissue (block or 15-20 unstained slides) available, or be willing to undergo an incisional or excisional lymph node biopsy of accessible adenopathy (or, in less accessible lymph nodes, 4 to 8 core biopsies).
* At least 1 measurable (≥ 2 cm in longest dimension) lesion on CT scan or magnetic resonance imaging (MRI).
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

Exclusion Criteria:

* Transformed DLBCL or DLBCL with coexistent histologies (eg, follicular or mucosa-associated lymphoid tissue lymphoma).
* Primary mediastinal (thymic) large B-cell lymphoma.
* Known central nervous system lymphoma (either primary or metastatic).
* Allogeneic stem cell transplant within the previous 6 months, or active graft versus host disease following allogeneic transplant.
* Use of immunosuppressive therapy within 28 days of starting study treatment. Immunosuppressive therapy includes but is not limited to cyclosporine A, tacrolimus, or high-dose corticosteroids. Subjects receiving corticosteroids must be at a dose level ≤ 10 mg/day within 7 days of initiating study treatment.
* Prior or concurrent therapy with a Janus kinase inhibitor or Bruton's tyrosine kinase inhibitor

Primary outcomes:
measure: Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to 285 days
measure: Phase 1: Number of Participants With Any Grade 3 or Higher TEAE
timeFrame: up to 285 days
measure: Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)
timeFrame: up to Day 28
measure: Phase 2: Objective Response Rate (ORR), Defined as the Percentage of Participants Achieving Either a Complete Response (CR) or a Partial Response (PR), Per the Modified Lugano Classification for Diffuse Large B-cell Lymphoma (DLBCL)
timeFrame: up to 1538 days
Secondary outcomes:
measure: Phase 1: ORR, Defined as the Percentage of Participants Achieving Either a CR or a PR, Per the Modified Lugano Classification for DLBCL
timeFrame: up to 250 days
measure: Phase 2: Duration of Response (DOR): Time From the First Overall Response Contributing to an Objective Response (CR or PR) to the Earlier of the Participant's Death and the First Overall Response of Progressive Disease, Per the Lugano Classification
timeFrame: up to 947 days
measure: Phase 2: Durable Response Rate (DRR)
timeFrame: up to 1538 days
measure: Phase 2: Progression-free Survival (PFS), Defined as the Time From the First Dose to the Earlier Date of Death Due to Any Cause or Disease Progression Determined by Objective Radiographic Disease Assessments
timeFrame: up to 1538 days
measure: Phase 2: Number of Participants With Any TEAE
timeFrame: up to 1573 days
measure: Phase 2: Number of Participants With Any Grade 3 or Higher TEAE
timeFrame: up to 1573 days
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: LAC-USC Medical Center/Kenneth Norris Jr Cancer Hospital
state: California
city: San Diego
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Augusta
country: United States
facility: Georgia Regents Research Institute
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Lansing
country: United States
facility: Michigan State University Breslin Cancer Center
state: Michigan
city: Billings
country: United States
facility: St Vincent Frontier Cancer Center
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Little Silver
country: United States
facility: Regional Cancer Center Associates, LLC
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Toledo
country: United States
facility: Toledo Clinic Cancer Centers
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Cancer Center
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Cancer Center
state: Texas
city: Puyallup
country: United States
facility: Northwest Medical Specialists & Research Institute
state: Washington
Study officials:
affiliation: Incyte Corporation
name: Peter Langmuir, MD
role: STUDY_DIRECTOR
References: