Study to Assess the Efficacy and Safety of Ublituximab and Umbralisib in Participants With Chronic Lymphocytic Leukemia (CLL) Currently Treated With Ibrutinib, Acalabrutinib or Venetoclax
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT04016805
- Lead Sponsor
- TG Therapeutics, Inc.
- Brief Summary
Phase 2, two cohort trial evaluating the addition of ublituximab and umbralisib on the rate of minimal residual disease (MRD) negativity in participants with Chronic Lymphocytic Leukemia (CLL), who are currently on treatment with ibrutinib, alacabrutinib or venetoclax.
- Detailed Description
This is a Phase 2 open label, two treatment cohort trial evaluating the addition of ublituximab and umbralisib on the rate of minimal residual disease (MRD) negativity in participants with CLL, who fail to achieve MRD negativity, after a minimum 6-month treatment with ibrutinib, alacabrutinib or venetoclax.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 41
- Participants with Chronic Lymphocytic Leukemia (CLL) who have been on treatment for at least 6 months
- Minimal Residual Disease positive at screening
- Adequate organ system function as specified in the protocol
- Ability to follow protocol procedures.
- Participants receiving cancer therapy or any investigational drug within 21 days of Cycle 1, Day 1.
- Participants with a known histological transformation
- Active Hepatitis B or Hepatitis C.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ublituximab + umbralisib + acalabrutinib Acalabrutinib Oral Capsule Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; acalabrutinib oral capsule every 12 hours (1 Cycle = 28 days). ublituximab + umbralisib + ibrutinib Umbralisib Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; ibrutinib oral tablet daily (1 Cycle = 28 days). ublituximab + umbralisib + ibrutinib Ublituximab Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; ibrutinib oral tablet daily (1 Cycle = 28 days). ublituximab + umbralisib + ibrutinib Ibrutinib Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; ibrutinib oral tablet daily (1 Cycle = 28 days). ublituximab + umbralisib + venetoclax Ublituximab Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; venetoclax oral tablet daily (1 Cycle = 28 days). ublituximab + umbralisib + venetoclax Umbralisib Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; venetoclax oral tablet daily (1 Cycle = 28 days). ublituximab + umbralisib + venetoclax Venetoclax Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; venetoclax oral tablet daily (1 Cycle = 28 days). ublituximab + umbralisib + acalabrutinib Umbralisib Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; acalabrutinib oral capsule every 12 hours (1 Cycle = 28 days). ublituximab + umbralisib + acalabrutinib Ublituximab Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; acalabrutinib oral capsule every 12 hours (1 Cycle = 28 days).
- Primary Outcome Measures
Name Time Method Rate of Undetected Minimal Residual Disease (U-MRD) Up to approximately 23 months U-MRD rate was defined as the proportion of participants who have undetectable MRD in the peripheral blood as confirmed by central lab.
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to approximately 34 months ORR was defined as percent of participants who achieve complete response (CR) or partial response (PR). CR was defined as no evidence of new disease, regression of all target nodal masses to normal size \< or = 1.5 cm in the longest diameter (LD) and an absolute lymphocyte count (ALC) in peripheral blood \< 4\*10\^9/L. PR was defined as no evidence of new disease, a decrease in peripheral blood ALC by ≥50% from baseline or a decrease to \<4 x 10\^9/L or a decrease by ≥50% from the baseline in the sum of the products (SPD) of the target nodal lesions or a decrease by ≥50% from baseline in the CLL marrow infiltrate or in B lymphoid, no target, splenic, liver, or non-target disease with worsening that meets the criteria for definitive nodules, peripheral blood counts with ANC \>1.5 x 10\^9/L or platelet count ≥100 x 10\^9/L or hemoglobin ≥110 g/L (11.0 g/dL) without red blood cell transfusions, all without need for exogenous growth factors.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events-Version (NCI-CTCAE-V5) Up to approximately 34 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. A TEAE is an AE that starts or worsens after receiving study drug.
Trial Locations
- Locations (1)
TG Therapeutics Investigational Trial Site
🇺🇸New York, New York, United States