A Phase 1 Trial of OPB-111077 in Combination With Bendamustine and Rituximab in Patients With r/r DLBCL

Study Overview
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Brief Summary
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To investigate the tolerability and safety of OPB-111077 in combination with bendamustine and rituximab in patients with r/r DLBCL.

Official Title
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A Phase 1, Multi-center, Open-label, Uncontrolled, Dose-escalation Trial to Evaluate the Safety of OPB-111077 in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Conditions
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Relapsed or Refractory Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: OPB-111077
* Drug: OPB-111077


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a definite diagnosis of Diffuse large B-cell lymphoma(DLBCL) Patients who have received at least initial standard treatment Patients with measurable lesions (based on International Working Group [IWG] 2014 criteria) Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 <Only for dose-expansion stage> Patients who are pathologically diagnosed as CD20 positive lymphoma Patients who have a history of being treated with 1 to 5 regimens of previous chemotherapy for the underlying disease Exclusion Criteria: Patients who are candidates for autologous or allogeneic hematopoietic stem cell transplantation Patients who were refractory to initial standard treatment Patients who have a history of bendamustine administration and are intolerant to bendamustine Patients with central nervous system (CNS) involvement of lymphoma or with a history of CNS involvement of lymphoma Patients diagnosed with DLBCL transformed from low-grade B-cell non-Hodgkin's lymphoma (NHL) <Only for dose-expansion stage> - Patients who have a history of rituximab administration and are intolerant to rituximab

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Stage<br>The dose of OPB-111077 in the first cohort will be 200 mg/day, increasing as appropriate to 400 mg/day in the second cohort and then to 600 mg/day in the third cohort. | Drug: OPB-111077<br>* OPB-111077+bendamustine<br>|
| Experimental: Dose Expansion Stage<br>4 days on and 3days off of 21-day cycles of OPB-111077 Day 1 of 21-days cycles of rituximab Day 2 and 3 of 21-day cycles of bendamustine | Drug: OPB-111077<br>* OPB-111077+rituximab+bendamustine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | The tolerability of OPB-111077 in combination with bendamustine and rituximab | 23days | 
| Incidence of Adverse events(AEs) | Safety of OPB-111077 in combination with bendamustine and rituximab | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy based on International working group(IWG) Lugano response criteria for Non Hodgkin's lymphoma ( (NHL) (2014)) | Percentage of Participants with Complete Response based on International working group(IWG) Lugano response criteria for Non Hodgkin's lymphoma ( (NHL) (2014)) Percentage of Participants with Complete Response and Partial Response based on International working group(IWG) Lugano response criteria for Non Hodgkin's lymphoma ( (NHL) (2014)) | Last dose of study drug (up to 3 years) |