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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

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ublituximab
Umbralisib
Ibrutinib
Venetoclax
Acalabrutinib Oral Capsule
Sponsored by
TG Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring umbralisib, ublituximab, venetoclax, ibrutinib, CLL, acalabrutinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects 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:

  • Subjects receiving cancer therapy or any investigational drug within 21 days of Cycle 1, Day 1.
  • Subjects with a known histological transformation
  • Active Hepatitis B or Hepatitis C.

Sites / Locations

  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

ublituximab + umbralisib + ibrutinib

ublituximab + umbralisib + venetoclax

ublituximab + umbralisib + acalabrutinib

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
July 10, 2019
Last Updated
July 3, 2023
Sponsor
TG Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04016805
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Strategic/Business decision
Study Start Date
August 5, 2019 (Actual)
Primary Completion Date
May 22, 2022 (Actual)
Study Completion Date
May 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TG Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
umbralisib, ublituximab, venetoclax, ibrutinib, CLL, acalabrutinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ublituximab + umbralisib + ibrutinib
Arm Type
Experimental
Arm Description
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).
Arm Title
ublituximab + umbralisib + venetoclax
Arm Type
Experimental
Arm Description
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).
Arm Title
ublituximab + umbralisib + acalabrutinib
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Ublituximab
Other Intervention Name(s)
TG-1101
Intervention Description
recombinant chimeric anti-CD20 monoclonal antibody administered as an IV infusion
Intervention Type
Drug
Intervention Name(s)
Umbralisib
Other Intervention Name(s)
TGR-1202
Intervention Description
Phosphoinositide-3-kinase (PI3K) delta inhibitor Tablet form, to taken orally on a daily basis
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
Imbruvica
Intervention Description
Bruton Tyrosine Kinase (BTK) inhibitor Tablet form, to taken orally on a daily basis
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclexta
Intervention Description
BCL-2 inhibitor Tablet form, to be taken orally
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib Oral Capsule
Other Intervention Name(s)
Calquence
Intervention Description
Kinase inhibitor, capsule form, to be taken orally
Primary Outcome Measure Information:
Title
Rate of Undetected Minimal Residual Disease (U-MRD)
Description
U-MRD rate was defined as the proportion of participants who have undetectable MRD in the peripheral blood as confirmed by central lab.
Time Frame
Up to approximately 23 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to approximately 34 months
Title
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)
Description
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.
Time Frame
Up to approximately 34 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
TG Therapeutics Investigational Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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