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

Sponsor

TG Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04016805

Collaborator

(none)

Enrollment

Locations

Arms

51.9

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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 subjects with Chronic Lymphocytic Leukemia (CLL), who are currently on treatment with ibrutinib, alacabrutinib or venetoclax.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Ublituximab Drug: Umbralisib Drug: Ibrutinib Drug: Venetoclax Drug: Acalabrutinib Oral Capsule	Phase 2

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 subjects with CLL, who fail to achieve MRD negativity, after a minimum 6-month treatment with ibrutinib, alacabrutinib or venetoclax.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 5, 2019

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ublituximab + umbralisib + ibrutinib ublituximab: 900 mg; to be administered once every cycle through cycle 6, then every 3 cycles thereafter umbralisib: 800 mg; to be administered daily ibrutinib: dose tolerated by subject; to be administered daily	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 ublituximab: 900 mg; to be administered once every cycle through cycle 6, then every 3 cycles thereafter umbralisib: 800 mg; to be administered daily venetoclax: dose tolerated by subject; to be administered daily	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 ublituximab: 900 mg; to be administered once every cycle through cycle 6, then every 3 cycles thereafter umbralisib: 800 mg; to be administered daily acalabrutinib: previously tolerated dose; to be administered every 12 hours	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

Arm

Intervention/Treatment

Experimental: ublituximab + umbralisib + ibrutinib

ublituximab: 900 mg; to be administered once every cycle through cycle 6, then every 3 cycles thereafter umbralisib: 800 mg; to be administered daily ibrutinib: dose tolerated by subject; to be administered daily

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

ublituximab: 900 mg; to be administered once every cycle through cycle 6, then every 3 cycles thereafter umbralisib: 800 mg; to be administered daily venetoclax: dose tolerated by subject; to be administered daily

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

ublituximab: 900 mg; to be administered once every cycle through cycle 6, then every 3 cycles thereafter umbralisib: 800 mg; to be administered daily acalabrutinib: previously tolerated dose; to be administered every 12 hours

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

Outcome Measures

Primary Outcome Measures

Rate of minimal residual disease negativity [24 months]
Assess the rate of undetectable minimal residual disease (U-MRD)

Secondary Outcome Measures

Overall Response Rate [24 months]
Objective response in subjects treated on study
Adverse Events that are Related to Treatment [12 months]
Number of Participants With Treatment-Related Adverse Events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TG Therapeutics Investigational Trial Site	Boston	Massachusetts	United States	02114
2	TG Therapeutics Investigational Trial Site	Hackensack	New Jersey	United States	07601
3	TG Therapeutics Investigational Trial Site	New York	New York	United States	10065