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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04016805
• Other study ID #: UTX-TGR-208
• Status: Terminated
• Phase: Phase 2
• Start date: August 5, 2019
• Est. completion date: May 22, 2022

Study information

• Verified date: July 2023
• Source: TG Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: May 22, 2022
• Est. primary completion date: May 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Ublituximab
recombinant chimeric anti-CD20 monoclonal antibody administered as an IV infusion
• Umbralisib
Phosphoinositide-3-kinase (PI3K) delta inhibitor Tablet form, to taken orally on a daily basis
• Ibrutinib
Bruton Tyrosine Kinase (BTK) inhibitor Tablet form, to taken orally on a daily basis
• Venetoclax
BCL-2 inhibitor Tablet form, to be taken orally
• Acalabrutinib Oral Capsule
Kinase inhibitor, capsule form, to be taken orally

Locations

Country	Name	City	State
United States	TG Therapeutics Investigational Trial Site	Boston	Massachusetts
United States	TG Therapeutics Investigational Trial Site	Hackensack	New Jersey
United States	TG Therapeutics Investigational Trial Site	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
TG Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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