A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study Details
Study Description
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)
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: itacitinib + ibrutinib
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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:
Drug: ibrutinib
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Outcome Measures
Primary Outcome Measures
- Phase 1: Safety and tolerability as assessed by adverse events and changes in clinical and laboratory assessments [Screening through 35 days after end of treatment, estimated to be 12 months]
- Phase 2: Efficacy as assessed by objective response rate (ORR) [Weeks 8, 16, and every 16 weeks thereafter, estimated to be 12 months]
Defined as percentage of subjects achieving a complete response (CR) or partial response (PR) based on radiographic assessment.
Secondary Outcome Measures
- Phase 1: Efficacy as assessed by objective response rate (ORR) [Screening through 16 weeks]
Defined as percentage of subjects achieving a complete response (CR) or partial response (PR) based on radiographic assessment.
- Phase 2: Efficacy as assessed by duration of response (DOR) [Weeks 8, 16, and every 16 weeks thereafter, estimated to be 12 months]
Defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.
- Phase 2: Durable response rate [Screening through 16 weeks]
Durable response rate is defined as the percentage of subjects achieving a CR or PR for > 16 weeks.
- Phase 2: Efficacy as assessed by progression-free survival (PFS) [Weeks 8, 16, and every 16 weeks thereafter, estimated to be 12 months]
Defined as date of enrollment to earliest date of disease progression based on radiographic assessment or death due to any cause.
- Phase 2: Efficacy as assessed by overall survival (OS) [Every 12 weeks, estimated to be 12 months]
Defined as date of enrollment until death due to any cause.
- Phase 2: Number of treatment-emergent adverse events [Screening through 35 days after end of treatment, estimated to be 12 months]
Any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically documented diagnosis of DLBCL.
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Phase 1: any DLBCL subtype.
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Phase 2: activated B-cell or unclassifiable subtypes confirmed by immunohistochemistry using the Hans algorithm
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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.
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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.
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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).
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At least 1 measurable (≥ 2 cm in longest dimension) lesion on CT scan or magnetic resonance imaging (MRI).
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Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Exclusion Criteria:
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Transformed DLBCL or DLBCL with coexistent histologies (eg, follicular or mucosa-associated lymphoid tissue lymphoma).
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Primary mediastinal (thymic) large B-cell lymphoma.
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Known central nervous system lymphoma (either primary or metastatic).
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Allogeneic stem cell transplant within the previous 6 months, or active graft versus host disease following allogeneic transplant.
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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.
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Prior or concurrent therapy with a Janus kinase inhibitor or Bruton's tyrosine kinase inhibitor
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Mayo Clinic Arizona | Scottsdale | Arizona | United States | 85259 |
2 | City of Hope National Medical Center | Duarte | California | United States | 91010 |
3 | Pacific Shores Medical Group | Long Beach | California | United States | 90813 |
4 | LAC-USC Medical Center/Kenneth Norris Jr Cancer Hospital | Los Angeles | California | United States | 90033 |
5 | Moores UC San Diego Cancer Center | San Diego | California | United States | 92093 |
6 | Mount Sinai Comprehensive Cancer Center | Miami Beach | Florida | United States | 33140 |
7 | Georgia Regents Research Institute | Augusta | Georgia | United States | 30912 |
8 | University of Maryland Cancer Center | Baltimore | Maryland | United States | 21201 |
9 | University of Michigan Cancer Center | Ann Arbor | Michigan | United States | 48109 |
10 | Michigan State University Breslin Cancer Center | Lansing | Michigan | United States | 48910 |
11 | St Vincent Frontier Cancer Center | Billings | Montana | United States | 59102 |
12 | Comprehensive Cancer Center of Nevada | Las Vegas | Nevada | United States | 89169 |
13 | Regional Cancer Center Associates, LLC | Little Silver | New Jersey | United States | 07739 |
14 | Roswell Cancer Center | Buffalo | New York | United States | 14263 |
15 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
16 | Toledo Clinic Cancer Centers | Toledo | Ohio | United States | 43623 |
17 | Tulsa Cancer Center | Tulsa | Oklahoma | United States | 74146 |
18 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
19 | University of Pennsylvania Health System | Philadelphia | Pennsylvania | United States | 19104 |
20 | Houston Methodist Cancer Center | Houston | Texas | United States | 77030 |
21 | Northwest Medical Specialists & Research Institute | Puyallup | Washington | United States | 98373 |
Sponsors and Collaborators
- Incyte Corporation
Investigators
- Study Director: Peter Langmuir, MD, Incyte Corporation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- INCB 39110-206