Ublituximab + TGR-1202 Compared to Obinutuzumab + Chlorambucil in Participants With Untreated and Previously Treated Chronic Lymphocytic Leukemia
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT02612311
- Lead Sponsor
- TG Therapeutics, Inc.
- Brief Summary
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) participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 603
- Treatment naïve or previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
- Eastern Cooperative Oncology Group (ECOG) score of 0 to 2
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm C: Ublituximab Ublituximab Participants 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 cycles thereafter, until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months. Arm B: Obinutuzumab + Chlorambucil Chlorambucil Participants received Obinutuzumab 100 mg, IV on Day 1, 900 mg on Day 2, followed by 1000 mg on Days 8 and 15 of cycle 1 (cycle length = 28 days), Day 1 of Cycle 2-6 along with Chlorambucil 0.5 milligram per kilogram (mg/kg) tablet orally on Days 1 and 15 once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months. Arm A: Ublituximab + Umbralisib TGR-1202 Participants 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 cycles 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 87 months. Arm D: Umbralisib TGR-1202 Participants received umbralisib, 800 mg tablets, orally, once daily during each cycle (cycle length= 28 days) until removal from study or up to 87 months. Arm B: Obinutuzumab + Chlorambucil Obinutuzumab Participants received Obinutuzumab 100 mg, IV on Day 1, 900 mg on Day 2, followed by 1000 mg on Days 8 and 15 of cycle 1 (cycle length = 28 days), Day 1 of Cycle 2-6 along with Chlorambucil 0.5 milligram per kilogram (mg/kg) tablet orally on Days 1 and 15 once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months. Arm A: Ublituximab + Umbralisib Ublituximab Participants 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 cycles 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 87 months.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria From enrolment to the earlier of the first documentation of definitive disease progression (PD) or death (Up to 87 months) 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 centimetres (cm) in the longest diameter (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 grams per Liter (g/L) decrease from the highest on-study hemoglobin (Hgb).
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) Per iwCLL Criteria Up to 87 months ORR=percent of participants who achieve complete response (CR), complete response with incomplete marrow recovery (CRi), partial response (PR) or nodular partial response (nPR).CR: No evidence of new disease; Absolute lymphocyte count(ALC)\<4x10\^9/liter(L);Regression of all target nodal masses to ≤1.5cm in 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;ANC \>1.5x10\^9/L,platelets≥100x10\^9/L,Hgb≥110 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 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.CRi:for CR except with ANC\<1000/µL and/or platelets\<100.
Minimal Residual Disease (MRD) Negativity Rate From Cycle 6 until Cycle 15 (cycle length=28 days) up to approximately 81.5 months 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.
Complete Response (CR) Rate Up to 87 months The CR rate is defined as the percentage of participants with a best overall response of complete response (CR) or complete response with incomplete marrow recovery (CRi). CR: No evidence of new disease; Absolute lymphocyte count(ALC)\<4x10\^9/L; Regression of all target nodal masses to ≤1.5 cm in 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; ANC\>1.5x10\^9/L,platelets≥100x10\^9/L,hemoglobin (Hgb)≥110 g/L. CRi was as for CR except with ANC \<1000/µL and/or platelets \<100,000/µL.
Duration of Response (DOR) From first documentation of response to study treatment till disease progression/death (up to approximately 87 months) DOR is defined as the interval from the first documentation of CR, CRi, PR, or nPR to the earlier of the first documentation of definitive disease progression or death from any cause.
Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE) From first dose of study treatment up to end of study (up to approximately 87 months) 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.
Trial Locations
- Locations (1)
TG Therapeutics Investigational Trial Site
🇬🇧Wolverhampton, United Kingdom