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

NCT04016805 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: UTX-TGR-208
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

umbralisib; ublituximab; venetoclax; ibrutinib; CLL; acalabrutinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall Response Rate (ORR)

  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)

  Up to approximately 34 months

Study Arms (3)

ublituximab + umbralisib + ibrutinib

EXPERIMENTAL

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; Drug: Umbralisib; Drug: Ibrutinib

ublituximab + umbralisib + venetoclax

EXPERIMENTAL

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; Drug: Umbralisib; Drug: Venetoclax

ublituximab + umbralisib + acalabrutinib

EXPERIMENTAL

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; Drug: Umbralisib; Drug: Acalabrutinib Oral Capsule

Interventions

Ublituximab DRUG

* recombinant chimeric anti-CD20 monoclonal antibody * administered as an IV infusion

Also known as: TG-1101

ublituximab + umbralisib + acalabrutinib; ublituximab + umbralisib + ibrutinib; ublituximab + umbralisib + venetoclax

Umbralisib DRUG

* Phosphoinositide-3-kinase (PI3K) delta inhibitor * Tablet form, to taken orally on a daily basis

Also known as: TGR-1202

ublituximab + umbralisib + acalabrutinib; ublituximab + umbralisib + ibrutinib; ublituximab + umbralisib + venetoclax

Ibrutinib DRUG

* Bruton Tyrosine Kinase (BTK) inhibitor * Tablet form, to taken orally on a daily basis

Also known as: Imbruvica

ublituximab + umbralisib + ibrutinib

Venetoclax DRUG

* BCL-2 inhibitor * Tablet form, to be taken orally

Also known as: Venclexta

ublituximab + umbralisib + venetoclax

Acalabrutinib Oral Capsule DRUG

Kinase inhibitor, capsule form, to be taken orally

Also known as: Calquence

ublituximab + umbralisib + acalabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• TG Therapeutics, Inc.: lead

Study Sites (3)

TG Therapeutics Investigational Trial Site

Boston, Massachusetts, 02114, United States

Location

TG Therapeutics Investigational Trial Site

Hackensack, New Jersey, 07601, United States

Location

TG Therapeutics Investigational Trial Site

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ublituximab; umbralisib; ibrutinib; venetoclax; acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Due to sponsor's business decision, the clinical trial was terminated by the sponsor prematurely. No analysis was done at the termination of the trial, therefore, outcome, and safety data are not available and the numbers of participants analyzed are reported as "0".

Results Point of Contact

• Title: TG Therapeutics Clinical Support Team
• Organization: TG Therapeutics

clinicalsupport@tgtxinc.com

1-877-575-8489

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 11, 2019
• Study Start: August 5, 2019
• Primary Completion: May 22, 2022
• Study Completion: May 22, 2022
• Last Updated: July 24, 2023
• Results First Posted: July 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

US (3)