Ublituximab + TGR-1202 Compared to Obinutuzumab + Chlorambucil in Participants With Untreated and Previously Treated Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

— UNITY-CLL  

Official title:

Phase 3, Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination With TGR-1202 (Umbralisib) Compared to Obinutuzumab in Combination With Chlorambucil in Patients With Chronic Lymphocytic Leukemia (CLL)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02612311
• Other study ID #: UTX-TGR-304
• Secondary ID: 2015-005758-36
• Status: Terminated
• Phase: Phase 3
• Start date: November 19, 2015
• Est. completion date: February 22, 2023

Study information

• Verified date: April 2024
• Source: TG Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the combination of ublituximab, a novel monoclonal antibody, and TGR-1202, a novel PI3K delta inhibitor compared to obinutuzumab and chlorambucil, and compared to ublituximab or TGR-1202 alone in Chronic Lymphocytic Leukemia (CLL) participants.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 603
• Est. completion date: February 22, 2023
• Est. primary completion date: February 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Treatment naïve or previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment

• Eastern Cooperative Oncology Group (ECOG) score of 0 to 2

Exclusion Criteria:

• Any major surgery, chemotherapy or immunotherapy within the last 21 days

• Evidence of hepatitis B virus, hepatitis C virus or known HIV infection

• Autologous hematologic stem cell transplant within 3 months of study entry. Prior Allogeneic hematologic stem cell transplant is excluded

• Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation)

• Prior therapy with obinutuzumab and/or chlorambucil or a PI3K delta inhibitor

Related Conditions & MeSH terms

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

Intervention

Biological:
• Obinutuzumab
Obinutuzumab: IV infusion
• Ublituximab
Ublituximab: IV infusion

Drug:
• TGR-1202
TGR-1202: Oral daily dose
• Chlorambucil
Chlorambucil: Oral dose

Locations

Country	Name	City	State
Israel	TG Therapeutics Investigational Trial Site	Ashkelon
Israel	TG Therapeutics Investigational Trial Site	Be'er Sheva
Israel	TG Therapeutics Investigational Trial Site	Haifa
Israel	TG Therapeutics Investigational Trial Site	Jerusalem
Israel	TG Therapeutics Investigational Trial Site	Nahariya
Israel	TG Therapeutics Investigational Trial Site	Petah tikva
Israel	TG Therapeutics Investigational Trial Site	Tel Aviv
Italy	TG Therapeutics Investigational Trial Site	Bologna
Italy	TG Therapeutics Investigational Trial Site	Ferrara
Italy	TG Therapeutics Investigational Trial Site	Milan
Italy	TG Therapeutics Investigational Trial Site	Rome
Italy	TG Therapeutics Investigational Trial Site	Torino
Poland	TG Therapeutics Investigational Trial Site	Chorzów
Poland	TG Therapeutics Investigational Trial Site	Gdynia
Poland	TG Therapeutics Investigational Trial Site	Krakow
Poland	TG Therapeutics Investigational Trial Site	Lódz
Poland	TG Therapeutics Investigational Trial Site	Lublin
Poland	TG Therapeutics Investigational Trial Site	Slupsk
Poland	TG Therapeutics Investigational Trial Site	Warszawa
Poland	TG Therapeutics Investigational Trial Site	Wroclaw
Russian Federation	TG Therapeutics Investigational Trial Site	Krasnozatonskiy
Russian Federation	TG Therapeutics Investigational Trial Site	Moscow
Russian Federation	TG Therapeutics Investigational Trial Site	Perm
Russian Federation	TG Therapeutics Investigational Trial Site	Petrozavodsk
Russian Federation	TG Therapeutics Investigational Trial Site	Rodionova
Russian Federation	TG Therapeutics Investigational Trial Site	Saint Petersburg
Russian Federation	TG Therapeutics Investigational Trial Site	Smolensk
Russian Federation	TG Therapeutics Investigational Trial Site	Tula
Russian Federation	TG Therapeutics Investigational Trial Site	Yaroslavl
Spain	TG Therapeutics Investigational Trial Site	Barcelona
Spain	TG Therapeutics Investigational Trial Site	Madrid
Spain	TG Therapeutics Investigational Trial Site	Valencia
United Kingdom	TG Therapeutics Investigational Trial Site	Cambridge
United Kingdom	TG Therapeutics Investigational Trial Site	Cumbria
United Kingdom	TG Therapeutics Investigational Trial Site	Dudley West
United Kingdom	TG Therapeutics Investigational Trial Site	London
United Kingdom	TG Therapeutics Investigational Trial Site	Northbrook
United Kingdom	TG Therapeutics Investigational Trial Site	Northumbria
United Kingdom	TG Therapeutics Investigational Trial Site	Norwich
United Kingdom	TG Therapeutics Investigational Trial Site	Peterborough
United Kingdom	TG Therapeutics Investigational Trial Site	Southampton
United Kingdom	TG Therapeutics Investigational Trial Site	St. James
United Kingdom	TG Therapeutics Investigational Trial Site	Sunderland
United Kingdom	TG Therapeutics Investigational Trial Site	Wolverhampton
United States	TG Therapeutics Investigational Trial Site	Albany	Georgia
United States	TG Therapeutics Investigational Trial Site	Ames	Iowa
United States	TG Therapeutics Investigational Trial Site	Ann Arbor	Michigan
United States	TG Therapeutics Investigational Trial Site	Aurora	Colorado
United States	TG Therapeutics Investigational Trial Site	Austin	Texas
United States	TG Therapeutics Investigational Trial Site	Baltimore	Maryland
United States	TG Therapeutics Investigational Trial Site	Baltimore	Maryland
United States	TG Therapeutics Investigational Trial Site	Bedford	Texas
United States	TG Therapeutics Investigational Trial Site	Bethesda	Maryland
United States	TG Therapeutics Investigational Trial Site	Blacksburg	Virginia
United States	TG Therapeutics Investigational Trial Site	Boca Raton	Florida
United States	TG Therapeutics Investigational Trial Site	Boston	Massachusetts
United States	TG Therapeutics Investigational Trial Site	Bridgeport	Connecticut
United States	TG Therapeutics Investigational Trial Site	Camp Hill	Pennsylvania
United States	TG Therapeutics Investigational Trial Site	Canton	Ohio
United States	TG Therapeutics Investigational Trial Site	Cedar Rapids	Iowa
United States	TG Therapeutics Investigational Trial Site	Chandler	Arizona
United States	TG Therapeutics Investigational Trial Site	Charlotte	North Carolina
United States	TG Therapeutics Investigational Trial Site	Charlottesville	Virginia
United States	TG Therapeutics Investigational Trial Site	Chattanooga	Tennessee
United States	TG Therapeutics Investigational Trial Site	Chicago	Illinois
United States	TG Therapeutics Investigational Trial Site	Cincinnati	Ohio
United States	TG Therapeutics Investigational Trial Site	Columbia	Missouri
United States	TG Therapeutics Investigational Trial Site	Columbia	Maryland
United States	TG Therapeutics Investigational Trial Site	Concord	California
United States	TG Therapeutics Investigational Trial Site	Danville	Pennsylvania
United States	TG Therapeutics Investigational Trial Site	Decatur	Illinois
United States	TG Therapeutics Investigational Trial Site	Denver	Colorado
United States	TG Therapeutics Investigational Trial Site	Detroit	Michigan
United States	TG Therapeutics Investigational Trial Site	Duarte	California
United States	TG Therapeutics Investigational Trial Site	Durham	North Carolina
United States	TG Therapeutics Investigational Trial Site	Durham	North Carolina
United States	TG Therapeutics Investigational Trial Site	East Setauket	New York
United States	TG Therapeutics Investigational Trial Site	Fayetteville	Arkansas
United States	TG Therapeutics Investigational Trial Site	Fort Belvoir	Virginia
United States	TG Therapeutics Investigational Trial Site	Fort Myers	Florida
United States	TG Therapeutics Investigational Trial Site	Fort Wayne	Indiana
United States	TG Therapeutics Investigational Trial Site	Fort Worth	Texas
United States	TG Therapeutics Investigational Trial Site	Glens Falls	New York
United States	TG Therapeutics Investigational Trial Site	Greenbrae	California
United States	TG Therapeutics Investigational Trial Site	Greenville	South Carolina
United States	TG Therapeutics Investigational Trial Site	Hershey	Pennsylvania
United States	TG Therapeutics Investigational Trial Site	Hickory	North Carolina
United States	TG Therapeutics Investigational Trial Site	Houston	Texas
United States	TG Therapeutics Investigational Trial Site	Huntsville	Alabama
United States	TG Therapeutics Investigational Trial Site	Indianapolis	Indiana
United States	TG Therapeutics Investigational Trial Site	Jackson	Michigan
United States	TG Therapeutics Investigational Trial Site	Jacksonville	Florida
United States	TG Therapeutics Investigational Trial Site	Jacksonville	Florida
United States	TG Therapeutics Investigational Trial Site	Kansas City	Kansas
United States	TG Therapeutics Investigational Trial Site	Kansas City	Missouri
United States	TG Therapeutics Investigational Trial Site	Kinston	North Carolina
United States	TG Therapeutics Investigational Trial Site	Las Vegas	Nevada
United States	TG Therapeutics Investigational Trial Site	Lebanon	New Hampshire
United States	TG Therapeutics Investigational Trial Site	Lincoln	Nebraska
United States	TG Therapeutics Investigational Trial Site	Louisville	Kentucky
United States	TG Therapeutics Investigational Trial Site	Macon	Georgia
United States	TG Therapeutics Investigational Trial Site	Maywood	Illinois
United States	TG Therapeutics Investigational Trial Site	Milwaukee	Wisconsin
United States	TG Therapeutics Investigational Trial Site	Mobile	Alabama
United States	TG Therapeutics Investigational Trial Site	Morristown	New Jersey
United States	TG Therapeutics Investigational Trial Site	Nashville	Tennessee
United States	TG Therapeutics Investigational Trial Site	New Haven	Connecticut
United States	TG Therapeutics Investigational Trial Site	Newark	Delaware
United States	TG Therapeutics Investigational Trial Site	Niles	Illinois
United States	TG Therapeutics Investigational Trial Site	Ocala	Florida
United States	TG Therapeutics Investigational Trial Site	Ogden	Utah
United States	TG Therapeutics Investigational Trial Site	Olympia	Washington
United States	TG Therapeutics Investigational Trial Site	Pawtucket	Rhode Island
United States	TG Therapeutics Investigational Trial Site	Pensacola	Florida
United States	TG Therapeutics Investigational Trial Site	Peoria	Illinois
United States	TG Therapeutics Investigational Trial Site	Philadelphia	Pennsylvania
United States	TG Therapeutics Investigational Trial Site	Phoenix	Arizona
United States	TG Therapeutics Investigational Trial Site	Pismo Beach	California
United States	TG Therapeutics Investigational Trial Site	Pittsburgh	Pennsylvania
United States	TG Therapeutics Investigational Trial Site	Pittsburgh	Pennsylvania
United States	TG Therapeutics Investigational Trial Site	Pleasanton	California
United States	TG Therapeutics Investigational Trial Site	Portland	Oregon
United States	TG Therapeutics Investigational Trial Site	Portland	Oregon
United States	TG Therapeutics Investigational Trial Site	Raleigh	North Carolina
United States	TG Therapeutics Investigational Trial Site	Saint Louis Park	Minnesota
United States	TG Therapeutics Investigational Trial Site	Saint Petersburg	Florida
United States	TG Therapeutics Investigational Trial Site	San Antonio	Texas
United States	TG Therapeutics Investigational Trial Site	San Antonio	Texas
United States	TG Therapeutics Investigational Trial Site	San Diego	California
United States	TG Therapeutics Investigational Trial Site	Santa Barbara	California
United States	TG Therapeutics Investigational Trial Site	Seattle	Washington
United States	TG Therapeutics Investigational Trial Site	Seattle	Washington
United States	TG Therapeutics Investigational Trial Site	Sioux Falls	South Dakota
United States	TG Therapeutics Investigational Trial Site	Somerville	New Jersey
United States	TG Therapeutics Investigational Trial Site	Spokane	Washington
United States	TG Therapeutics Investigational Trial Site	Springfield	Oregon
United States	TG Therapeutics Investigational Trial Site	Stamford	Connecticut
United States	TG Therapeutics Investigational Trial Site	Swansea	Illinois
United States	TG Therapeutics Investigational Trial Site	Syracuse	New York
United States	TG Therapeutics Investigational Trial Site	Tallahassee	Florida
United States	TG Therapeutics Investigational Trial Site	Tampa	Florida
United States	TG Therapeutics Investigational Trial Site	Toledo	Ohio
United States	TG Therapeutics Investigational Trial Site	Tucson	Arizona
United States	TG Therapeutics Investigational Trial Site	Tyler	Texas
United States	TG Therapeutics Investigational Trial Site	Urbana	Illinois
United States	TG Therapeutics Investigational Trial Site	Vancouver	Washington
United States	TG Therapeutics Investigational Trial Site	Washington	North Carolina
United States	TG Therapeutics Investigational Trial Site	Watertown	South Dakota
United States	TG Therapeutics Investigational Trial Site	Wauwatosa	Wisconsin
United States	TG Therapeutics Investigational Trial Site	West Palm Beach	Florida
United States	TG Therapeutics Investigational Trial Site	Westwood	Kansas
United States	TG Therapeutics Investigational Trial Site	Whittier	California
United States	TG Therapeutics Investigational Trial Site	Worcester	Massachusetts
United States	TG Therapeutics Investigational Trial Site	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
TG Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria	PFS was defined as the interval from enrollment to the earlier of the first documentation of definitive disease progression (PD) or death from any cause. PD was appearance of new nodes >1.5 centimetres (cm) in the longest diameter (LD) and >1.0 in longest perpendicular diameter (LPD), new or recurrent hepatomegaly or splenomegaly, new or reappearance of an unequivocal extra-nodal lesion, =50% increase from the nadir in the sum of products of diameters (SPD) of target lesions, =50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of =50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 grams per Liter (g/L) decrease from the highest on-study hemoglobin (Hgb).	From enrolment to the earlier of the first documentation of definitive disease progression (PD) or death (Up to 87 months)
Secondary	Overall Response Rate (ORR) Per iwCLL Criteria	ORR=percent of participants who achieve complete response (CR), complete response with incomplete marrow recovery (CRi), partial response (PR) or nodular partial response (nPR).CR: No evidence of new disease; Absolute lymphocyte count(ALC)<4x10^9/liter(L);Regression of all target nodal masses to =1.5cm in LD;Normal spleen,liver size;Regression to normal of all nodal non-target disease and disappearance of all detectable;Non-nodal,non-target disease;Morphologically negative bone marrow;No lymphoid nodules;ANC >1.5x10^9/L,platelets=100x10^9/L,Hgb=110 g/L.PR:No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC<4x10^9/L or =50% decrease from baseline in sum of products of target nodal lesions;splenomegaly; hepatomegaly;=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules;response in any 1: ANC>1.5x10^9/L, platelets>100x10^9/L,Hgb>110g/L or =50% increase over baseline in any of these.CRi:for CR except with ANC<1000/µL and/or platelets<100.	Up to 87 months
Secondary	Complete Response (CR) Rate	The CR rate is defined as the percentage of participants with a best overall response of complete response (CR) or complete response with incomplete marrow recovery (CRi). CR: No evidence of new disease; Absolute lymphocyte count(ALC)<4x10^9/L; Regression of all target nodal masses to =1.5 cm in LD; Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC>1.5x10^9/L,platelets=100x10^9/L,hemoglobin (Hgb)=110 g/L. CRi was as for CR except with ANC <1000/µL and/or platelets <100,000/µL.	Up to 87 months
Secondary	Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate is defined as the percentage of participants who are MRD negative. If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow.	From Cycle 6 until Cycle 15 (cycle length=28 days) up to approximately 81.5 months
Secondary	Duration of Response (DOR)	DOR is defined as the interval from the first documentation of CR, CRi, PR, or nPR to the earlier of the first documentation of definitive disease progression or death from any cause.	From first documentation of response to study treatment till disease progression/death (up to approximately 87 months)
Secondary	Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)	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. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related.	From first dose of study treatment up to end of study (up to approximately 87 months)