Ublituximab in Combination With TGR-1202 +/- Ibrutinib or Bendamustine in Patients With B-cell Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of Ublituximab in combination with TGR-1202, with or without ibrutinib or bendamustine, in patients with advanced hematologic malignancies

Official Title
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A Phase I/Ib Study Evaluating the Efficacy and Safety of Ublituximab, a Third-Generation Anti-CD20 Monoclonal Antibody, in Combination With TGR-1202, a Novel PI3k Delta Inhibitor; and Ibrutinib or Bendamustine, in Patients With B-cell Malignancies.

Conditions
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Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Ublituximab + TGR-1202
* Drug: Ublituximab + TGR-1202 + ibrutinib
* Drug: Ublituximab + TGR-1202 + bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and other B-cell lymphoproliferative disorders as approved by the Medical Monitor or Study Chair Refractory to or relapsed after at least 1 prior treatment regimen Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 Exclusion Criteria: Any major surgery, chemotherapy or immunotherapy within the last 21 days Known hepatitis B virus, hepatitis C virus or HIV infection Autologous hematologic stem cell transplant within 3 months of study entry or Allogeneic hematologic stem cell transplant within 12 months Primary central nervous system lymphoma or known intracranial involvement

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ublituximab + TGR-1202<br>Ublituximab at a fixed IV infusion dose Days 1, 8 and 15 followed by maintenance infusions TGR-1202 oral daily dose | Drug: Ublituximab + TGR-1202<br>* Ublituximab IV infusion TGR-1202 oral daily dose<br>|
| Experimental: Ublituximab + TGR-1202 + ibrutinib<br>Ublituximab at a fixed IV infusion dose Days 1, 8 and 15 followed by maintenance infusions TGR-1202 oral daily dose ibrutinib oral daily dose | Drug: Ublituximab + TGR-1202 + ibrutinib<br>* Ublituximab IV infusion TGR-1202 oral daily dose Ibrutinib oral daily dose<br>* Other names: Imbruvica;|
| Experimental: Ublituximab + TGR-1202 + bendamustine<br>Ublituximab at a fixed IV infusion dose Days 1, 8 and 15 followed by maintenance infusions TGR-1202 oral daily dose Bendamustine at a fixed IV infusion on Days 1 & 2 | Drug: Ublituximab + TGR-1202 + bendamustine<br>* Ublituximab IV infusion TGR-1202 oral daily dose Bendamustine IV infusion<br>* Other names: Treanda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose acceptable for participants | To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities | 28 days (1 cycle of therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To assess the overall response rate (ORR) in patients with hematologic malignancies treated with Ublituximab in combination with TGR-1202 | Up to 1 year |