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

A Phase 2 Study to Assess the Efficacy and Safety of Ublituximab and Umbralisib in Subjects With Chronic Lymphocytic Leukemia (CLL) Currently Treated With Ibrutinib, Acalabrutinib or Venetoclax

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Ublituximab; Drug: Umbralisib; Drug: Ibrutinib; Drug: Venetoclax; Drug: Acalabrutinib Oral Capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • TG Therapeutics Investigational Trial Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • TG Therapeutics Investigational Trial Site
  • New York
    • New York, New York, United States, 10065
      • TG Therapeutics Investigational Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ublituximab + umbralisib + 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).	Drug: Ublituximab; recombinant chimeric anti-CD20 monoclonal antibody; administered as an IV infusion; Other Names: TG-1101; Drug: Umbralisib; Phosphoinositide-3-kinase (PI3K) delta inhibitor; Tablet form, to taken orally on a daily basis; Other Names: TGR-1202; Drug: Ibrutinib; Bruton Tyrosine Kinase (BTK) inhibitor; Tablet form, to taken orally on a daily basis; Other Names: Imbruvica
Experimental: ublituximab + umbralisib + 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).	Drug: Ublituximab; recombinant chimeric anti-CD20 monoclonal antibody; administered as an IV infusion; Other Names: TG-1101; Drug: Umbralisib; Phosphoinositide-3-kinase (PI3K) delta inhibitor; Tablet form, to taken orally on a daily basis; Other Names: TGR-1202; Drug: Venetoclax; BCL-2 inhibitor; Tablet form, to be taken orally; Other Names: Venclexta
Experimental: ublituximab + umbralisib + acalabrutinib; 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).	Drug: Ublituximab; recombinant chimeric anti-CD20 monoclonal antibody; administered as an IV infusion; Other Names: TG-1101; Drug: Umbralisib; Phosphoinositide-3-kinase (PI3K) delta inhibitor; Tablet form, to taken orally on a daily basis; Other Names: TGR-1202; Drug: Acalabrutinib Oral Capsule; Kinase inhibitor, capsule form, to be taken orally; Other Names: Calquence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Undetected Minimal Residual Disease (U-MRD)	U-MRD rate was defined as the proportion of participants who have undetectable MRD in the peripheral blood as confirmed by central lab.	Up to approximately 23 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	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.	Up to approximately 34 months
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)	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.	Up to approximately 34 months

Collaborators and Investigators

• Sponsor: TG Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2019
• Primary Completion (Actual): May 22, 2022
• Study Completion (Actual): May 22, 2022

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: CLL; venetoclax; ibrutinib; acalabrutinib; umbralisib; ublituximab
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, B-Cell; Chronic Disease; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Venetoclax; Acalabrutinib
• Other Study ID Numbers: UTX-TGR-208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No