Ublituximab + TGR-1202 Compared to Obinutuzumab + Chlorambucil in Patients With Untreated and Previously Treated Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This study evaluates the combination of ublituximab, a novel monoclonal antibody, and TGR-1202, a novel PI3K delta inhibitor compared to obinutuzumab and chlorambucil, and compared to ublituximab or TGR-1202 alone in Chronic Lymphocytic Leukemia (CLL) patients.

Official Title
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A Phase 3, Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination With TGR-1202 Compared to Obinutuzumab in Combination With Chlorambucil in Patients With Chronic Lymphocytic Leukemia (CLL)

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Biological: Obinutuzumab
* Biological: Ublituximab
* Drug: TGR-1202
* Drug: Chlorambucil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment naïve or previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 Exclusion Criteria: Any major surgery, chemotherapy or immunotherapy within the last 21 days Evidence of hepatitis B virus, hepatitis C virus or known HIV infection Autologous hematologic stem cell transplant within 3 months of study entry. Prior Allogeneic hematologic stem cell transplant is excluded Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation) Prior therapy with obinutuzumab and/or chlorambucil or a PI3K delta inhibitor

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ublituximab + TGR-1202<br>Ublituximab: IV infusion dose on Days 1, 8 and 15 followed by maintenance infusions TGR-1202: Fixed oral daily dose | Biological: Ublituximab<br>* Ublituximab: IV infusion<br>Drug: TGR-1202<br>* TGR-1202: Oral daily dose<br>|
| Active Comparator: Obinutuzumab + Chlorambucil<br>Obinutuzumab: IV infusion dose on Days 1, 8 and 15 in Cycle 1 followed by Day 1 infusion in Cycles 2 - 6 Chlorambucil: Oral dose on Days 1 and 15 of Cycles 1 - 6 | Biological: Obinutuzumab<br>* Obinutuzumab: IV infusion<br>* Other names: GAZYVA;Drug: Chlorambucil<br>* Chlorambucil: Oral dose<br>* Other names: Leukeran;|
| Experimental: Ublituximab<br>- Ublituximab: IV infusion dose on Days 1, 8 and 15 followed by maintenance infusions | Biological: Ublituximab<br>* Ublituximab: IV infusion<br>|
| Experimental: TGR-1202<br>- TGR-1202: Fixed oral daily dose | Drug: TGR-1202<br>* TGR-1202: Oral daily dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | To assess the progression-free survival (PFS) in patients with Chronic Lymphocytic Leukemia treated with ublituximab in combination with TGR-1202 compared to obinutuzumab + chlorambucil | From date of randomization until the date of first documented progression, assessed up through 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To assess the overall response rate (ORR) in patients with Chronic Lymphocytic Leukemia treated with ublituximab + TGR-1202 compared to ublituximab and TGR-1202 alone | Every 12 weeks up to 2 years |