Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)

Study Overview
=================
Brief Summary
-----------------
ULTRA-V: Study to Assess the Efficacy and Safety of Ublituximab in Combination with Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects with Chronic Lymphocytic Leukemia (CLL)

Detailed Description
-----------------
This is an open-label, multicenter, Phase 2/3 study to evaluate the efficacy and safety of the combination of ublituximab + umbralisib + venetoclax (U2-V) compared to the combination of ublituximab + umbralisib (U2) in patients with either treatment naïve or previously treated CLL/ small lymphocytic lymphoma (SLL)

Official Title
-----------------
Phase 2/3 Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects With Chronic Lymphocytic Leukemia (CLL)

Conditions
-----------------
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
-----------------
* Drug: Ublituximab
* Drug: Umbralisib
* Drug: Venetoclax


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that warrants treatment Adequate organ system function as specified in the protocol Ability to follow protocol procedures. Exclusion Criteria: Subjects receiving cancer therapy or any investigational drug within 21 days of Cycle 1, Day 1 Prior exposure to any PI3K inhibitor or venetoclax Autologous hematologic stem cell transplant within 6 months of study entry. Prior allogeneic hematologic stem cell transplant is excluded Active Hepatitis B or Hepatitis C.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2: Previously Treated CLL (BTK-Not Refractory)<br> | Drug: Ublituximab<br>* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form<br>* Other names: UKONIQ;Drug: Venetoclax<br>* B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally<br>* Other names: Venclexta®;|
| Experimental: Phase 2: Previously Treated CLL (BTK-Refractory)<br> | Drug: Ublituximab<br>* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form<br>* Other names: UKONIQ;Drug: Venetoclax<br>* B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally<br>* Other names: Venclexta®;|
| Experimental: Phase 2: Treatment Naïve CLL<br> | Drug: Ublituximab<br>* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form<br>* Other names: UKONIQ;Drug: Venetoclax<br>* B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally<br>* Other names: Venclexta®;|
| Experimental: Phase 3: Treatment Naïve CLL/SLL: Ublituximab + Umbralisib + Venetoclax (U2-V)<br> | Drug: Ublituximab<br>* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form<br>* Other names: UKONIQ;Drug: Venetoclax<br>* B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally<br>* Other names: Venclexta®;|
| Experimental: Phase 3: Treatment Naïve CLL/SLL: Ublituximab + Umbralisib (U2)<br> | Drug: Ublituximab<br>* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form<br>* Other names: UKONIQ;|
| Experimental: Phase 3: Previously Treated CLL/SLL: Ublituximab + Umbralisib + Venetoclax (U2-V)<br> | Drug: Ublituximab<br>* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form<br>* Other names: UKONIQ;Drug: Venetoclax<br>* B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally<br>* Other names: Venclexta®;|
| Experimental: Phase 3: Previously Treated CLL/SLL: Ublituximab + Umbralisib (U2)<br> | Drug: Ublituximab<br>* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form<br>* Other names: UKONIQ;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: Complete Response (CR) Rate |  | Up to 12 months | 
| Phase 2: Overall Response Rate |  | Up to 12 months | 
| Phase 3: Progression-Free Survival | Progression-Free Survival in subjects treated with U2-V compared with U2 | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events That Are Related to Treatment | Number of Participants With Treatment-Related Adverse Event and any potential abnormal laboratory results | 6 months of therapy | 
| Phase 3: Overall Response Rate | Objective response in subjects treated with ublituximab + umbralisib + venetoclax | Up to 12 months | 
| Rate of Undetectable Minimal Residual Disease (MRD) |  | 60 months | 
| Phase 2: Time to Response (TTR) |  | Up to 12 months | 
| Phase 2: Duration of Response (DOR) |  | 60 months | 
| Phase 3: Complete Response (CR) Rate |  | Up to 12 months | 
| Phase 3: Overall Survival (OS) |  | 72 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CLL, SLL