A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
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
1 other identifier
interventional
33
1 country
21
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 lymphoma
Started Dec 2016
Typical duration for phase_1 lymphoma
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 2, 2016
CompletedFirst Posted
Study publicly available on registry
May 3, 2016
CompletedStudy Start
First participant enrolled
December 29, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 6, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 6, 2022
CompletedResults Posted
Study results publicly available
June 15, 2023
CompletedJune 15, 2023
June 1, 2023
5.4 years
May 2, 2016
May 15, 2023
June 9, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug.
up to 285 days
Phase 1: Number of Participants With Any Grade 3 or Higher TEAE
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated.
up to 285 days
Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)
A DLT was defined as the occurrence of any protocol-defined toxicities occurring up to and including Study Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria. In order to be included in the tolerability review, subjects must have received the cohort-specific dose of INCB039110 and ibrutinib for at least 75% of the days during the 28-day surveillance period or have experienced a DLT.
up to Day 28
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)
CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 centimeters (cm) in the longest dimension transverse diameter of lesion (LDi); (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: ≥50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 millimeters (mm) × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node \>5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by \>50% in length beyond normal; (4) no new lesions.
up to 1538 days
Secondary Outcomes (6)
Phase 1: ORR, Defined as the Percentage of Participants Achieving Either a CR or a PR, Per the Modified Lugano Classification for DLBCL
up to 250 days
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
up to 947 days
Phase 2: Durable Response Rate (DRR)
up to 1538 days
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
up to 1538 days
Phase 2: Number of Participants With Any TEAE
up to 1573 days
- +1 more secondary outcomes
Study Arms (1)
itacitinib + ibrutinib
EXPERIMENTALInterventions
Phase 1 will evaluate itacitinib at the protocol-specified starting dose, with a possible increase or decrease depending on tolerability. Phase 2 will evaluate the recommended dose determined in Phase 1.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
Mayo Clinic Arizona
Scottsdale, Arizona, 85259, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
Pacific Shores Medical Group
Long Beach, California, 90813, United States
LAC-USC Medical Center/Kenneth Norris Jr Cancer Hospital
Los Angeles, California, 90033, United States
Moores UC San Diego Cancer Center
San Diego, California, 92093, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140, United States
Georgia Regents Research Institute
Augusta, Georgia, 30912, United States
University of Maryland Cancer Center
Baltimore, Maryland, 21201, United States
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109, United States
Michigan State University Breslin Cancer Center
Lansing, Michigan, 48910, United States
St Vincent Frontier Cancer Center
Billings, Montana, 59102, United States
Comprehensive Cancer Center of Nevada
Las Vegas, Nevada, 89169, United States
Regional Cancer Center Associates, LLC
Little Silver, New Jersey, 07739, United States
Roswell Cancer Center
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Toledo Clinic Cancer Centers
Toledo, Ohio, 43623, United States
Tulsa Cancer Center
Tulsa, Oklahoma, 74146, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104, United States
Houston Methodist Cancer Center
Houston, Texas, 77030, United States
Northwest Medical Specialists & Research Institute
Puyallup, Washington, 98373, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Incyte Corporation
Study Officials
- STUDY DIRECTOR
Peter Langmuir, MD
Incyte Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 2, 2016
First Posted
May 3, 2016
Study Start
December 29, 2016
Primary Completion
June 6, 2022
Study Completion
June 6, 2022
Last Updated
June 15, 2023
Results First Posted
June 15, 2023
Record last verified: 2023-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
- Access Criteria
- Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency.