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

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)

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: ibrutinib; Drug: itacitinib

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90033
      • LAC-USC Medical Center/Kenneth Norris Jr Cancer Hospital
    • San Diego, California, United States, 92093
      • Moores UC San Diego Cancer Center
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Cancer Center
    • Lansing, Michigan, United States, 48910
      • Michigan State University Breslin Cancer Center
  • Montana
    • Billings, Montana, United States, 59102
      • St Vincent Frontier Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Center of Nevada
  • New Jersey
    • Little Silver, New Jersey, United States, 07739
      • Regional Cancer Center Associates, LLC
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Tulsa Cancer Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center
  • Washington
    • Puyallup, Washington, United States, 98373
      • Northwest Medical Specialists & Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: itacitinib + ibrutinib	Drug: ibrutinib; Drug: itacitinib; 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.; Other Names: INCB039110

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: ORR, Defined as the Percentage of Participants Achieving Either a CR or a PR, Per the Modified Lugano Classification for DLBCL	CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 cm in the 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 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 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	Disease progression requires ≥1 of the following: (1) an abnormal individual node/lesion with all of the following: (a) LDi > 1.5 cm; (b) increase by ≥50% from cross product of the LDi and the perpendicular diameter (PPD) nadir; (c) increase in LDi or the shortest axis perpendicular to the LDi (SDi) from nadir: (i) 0.5 cm for lesions ≤2 cm; (ii) 1.0 cm for lesions > 2 cm. (2) For splenomegaly, the splenic length must increased by 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, must increase by at least 2 cm from baseline. (3) New/recurrent splenomegaly. (4) New/clear progression of preexisting nonmeasured lesions. (5) Regrowth of previously resolved lesions. (6) A new node > 1.5 cm in any axis. (7) A new extranodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be unequivocal/attributable to lymphoma. (8) Assessable disease of any size unequivocally attributable to lymphoma. (9) New or recurrent involvement of the bone marrow.	up to 947 days
Phase 2: Durable Response Rate (DRR)	DRR=percentage of participants with a CR or PR, per Lugano Classification, for ≥16 weeks since the time from the first overall response contributing to an objective response (CR or PR). CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 cm in the 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 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
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	Disease progression requires ≥1 of the following: (1) an abnormal individual node/lesion with all of the following: (a) LDi > 1.5 cm; (b) increase by ≥50% from cross product of the LDi and the perpendicular diameter (PPD) nadir; (c) increase in LDi or the shortest axis perpendicular to the LDi (SDi) from nadir: (i) 0.5 cm for lesions ≤2 cm; (ii) 1.0 cm for lesions > 2 cm. (2) For splenomegaly, the splenic length must increased by 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, must increase by at least 2 cm from baseline. (3) New/recurrent splenomegaly. (4) New/clear progression of preexisting nonmeasured lesions. (5) Regrowth of previously resolved lesions. (6) A new node > 1.5 cm in any axis. (7) A new extranodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be unequivocal/attributable to lymphoma. (8) Assessable disease of any size unequivocally attributable to lymphoma. (9) New or recurrent involvement of the bone marrow.	up to 1538 days
Phase 2: Number of Participants With Any TEAE	An 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 1573 days
Phase 2: Number of Participants With Any Grade 3 or Higher TEAE	An 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 1573 days

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Peter Langmuir, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2016
• Primary Completion (Actual): June 6, 2022
• Study Completion (Actual): June 6, 2022

Study Registration Dates

• First Submitted: May 2, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimated): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: non-Hodgkin lymphoma; Diffuse large B-cell lymphoma; JAK1 inhibitor; Bruton's tyrosine kinase (BTK) inhibitor; Relapsed Diffuse large B-cell lymphoma; Refractory Diffuse large B-cell lymphoma; activated B cell; germinal center B-cell
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: INCB 39110-206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes