A Study to Evaluate the Safety and Efficacy of Ublituximab in Combination With Umbralisib for Participants Previously Enrolled in Protocol UTX-TGR-304

Study Overview
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Brief Summary
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The purpose of this study was to provide the opportunity to the participants who progressed on treatment arm previously in the study UTX-TGR-304 (NCT02612311) to receive ublituximab (TG-1101) treatment in combination with umbralisib (TGR-1202).

Official Title
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A Multi-Center, Open-Label, Compassionate Use Extension Study of Ublituximab (TG-1101) in Combination With Umbralisib (TGR-1202) for Patients Previously Enrolled in Protocol UTX-TGR-304

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Biological: Ublituximab
* Drug: Umbralisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior treatment in clinical trial UTX-TGR-304 Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 Exclusion Criteria: Participants refractory to ublituximab + TGR-1202 Transformation of chronic lymphocytic leukemia (CLL) to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation)

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parent Study Arm B<br>Participants from Arm B of the parent trial (UTX-TGR-304) received ublituximab, 150 milligrams (mg), intravenously (IV), on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 months thereafter, along with umbralisib, 800 mg, orally, once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 78 months. | Biological: Ublituximab<br>* Ublituximab IV infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* Umbralisib tablets<br>* Other names: TGR-1202;|
| Experimental: Parent Study Arm C<br>Participants from Arm C of the parent trial (UTX-TGR-304) received ublituximab, 900 mg, IV, on Day 1 of Cycles 1-6 (cycle length=28 days), and once every 3 months thereafter, along with umbralisib, 800 mg, orally, once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 78 months. | Biological: Ublituximab<br>* Ublituximab IV infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* Umbralisib tablets<br>* Other names: TGR-1202;|
| Experimental: Parent Study Arm D<br>Participants from Arm D of the parent trial (UTX-TGR-304) received ublituximab, 150 mg, IV, on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 months thereafter, along with umbralisib, 800 mg, orally, once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 78 months. | Biological: Ublituximab<br>* Ublituximab IV infusion<br>* Other names: TG-1101;Drug: Umbralisib<br>* Umbralisib tablets<br>* Other names: TGR-1202;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) as Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria | ORR was defined as sum of participants with partial responses (PR) and complete responses (CR). CR: No evidence of new disease; Absolute lymphocyte count(ALC)<4x10^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters (cm) in longest diameter(LD); Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; Absolute neutrophil count(ANC)>1.5x10^9/L,platelets≥100x10^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR: No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC<4x10^9/L or ≥50% decrease from baseline in sum of products(SPD) of target nodal lesions; splenomegaly; hepatomegaly;≥50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; response in any 1:ANC>1.5x10^9/L,platelets>100x10^9/L,Hgb>110g/L or ≥50% increase over baseline in any of these. | Up to 76 months | 
| Complete Response (CR) Rate Per iwCLL Criteria | The CR rate was defined as the percentage of participants who achieved CR. CR: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L. | Up to 76 months | 
| Progression-Free Survival (PFS) Per iwCLL Criteria | PFS was defined as the interval from enrollment to the earlier of the first documentation of definitive disease progression (PD) or death from any cause. PD was appearance of new nodes >1.5 cm in the LD and >1.0 in longest perpendicular diameter (LPD), new or recurrent hepatomegaly or splenomegaly, new or reappearance of an unequivocal extra-nodal lesion, ≥50% increase from the nadir in the sum of products of diameters (SPD) of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 g/L decrease from the highest on-study Hgb. | Up to 76 months | 
| Duration of Response (DOR) | DOR:Interval from first documentation of CR/PR to first documentation of PD or death from any cause.CR:ALC<4x10^9/L;Regression to normal of target nodal masses,nodal non-target disease,and no detectable non-nodal,non-target disease;Normal spleen,liver size;Morphologically negative bone marrow,No lymphoid nodules;ANC>1.5x10^9/L,Platelets≥100x10^9/L,Hgb≥110 g/L.PR:Response in 2 or more:ALC<4x10^9/L, ≥50% drop from baseline in ALC or SPD of target nodal lesions,Hepatosplenomegaly,≥50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules;Response in 1 or more:ANC>1.5x10^9/L,Platelets>100x10^9/L,Hgb>110 g/L or ≥50% increase over baseline in any.PD:Response in 1 or more:new nodes,Hepatosplenomegaly,unequivocal extra-nodal lesion;≥50% increase from nadir in SPD of target lesions or LD of node/extra-nodal mass or Splenic/Hepatic size,Unequivocal increase in non-target disease,More aggressive histology;Drop of >50% in platelets/>20g/L in Hgb from highest on-study count. | Up to 76 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal Residual Disease (MRD) Negativity Rate | MRD negativity rate is defined as the percentage of participants who are MRD negative. If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow. | From Cycle 6 until Cycle 15 (cycle length=28 days) (Up to approximately 76 months) | 
| Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related. | Up to 78 months |