Chronic Lymphocytic LeukemiaPhase 3UNITY-CLLNCT02612311

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

A Phase 3 study testing Obinutuzumab, Ublituximab and TGR-1202 in people with Chronic Lymphocytic Leukemia, run by TG Therapeutics, Inc. at 154 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Lymphocytic Leukemia
What is being tested?: Obinutuzumab, Ublituximab and TGR-1202
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 603 participants
Where: 154 sitesin 7 countries
Study dates: 19 Nov 2015to 22 Feb 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Treatment naïve or previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
Eastern Cooperative Oncology Group (ECOG) score of 0 to 2

Who cannot join

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

Trial locations and contacts

154 sites in 7 countries.

Country

City, postcode or hospital

154 sites in 7 countries

United States110 sites

TG Therapeutics Investigational Trial Site
Albany, Georgia, 31701
TG Therapeutics Investigational Trial Site
Ames, Iowa, 50010
TG Therapeutics Investigational Trial Site
Ann Arbor, Michigan, 48106
TG Therapeutics Investigational Trial Site
Aurora, Colorado, 80012
TG Therapeutics Investigational Trial Site
Austin, Texas, 78705
TG Therapeutics Investigational Trial Site
Baltimore, Maryland, 21202
TG Therapeutics Investigational Trial Site
Baltimore, Maryland, 21215
TG Therapeutics Investigational Trial Site
Bedford, Texas, 76022
TG Therapeutics Investigational Trial Site
Bethesda, Maryland, 20817
TG Therapeutics Investigational Trial Site
Blacksburg, Virginia, 24060
TG Therapeutics Investigational Trial Site
Boca Raton, Florida, 33486
TG Therapeutics Investigational Trial Site
Boston, Massachusetts, 02111
TG Therapeutics Investigational Trial Site
Bridgeport, Connecticut, 06606
TG Therapeutics Investigational Trial Site
Camp Hill, Pennsylvania, 17011
TG Therapeutics Investigational Trial Site
Canton, Ohio, 44718
TG Therapeutics Investigational Trial Site
Cedar Rapids, Iowa, 52403
TG Therapeutics Investigational Trial Site
Chandler, Arizona, 85224
TG Therapeutics Investigational Trial Site
Charlotte, North Carolina, 28204
TG Therapeutics Investigational Trial Site
Charlottesville, Virginia, 22908
TG Therapeutics Investigational Trial Site
Chattanooga, Tennessee, 37404
TG Therapeutics Investigational Trial Site
Chicago, Illinois, 60612
TG Therapeutics Investigational Trial Site
Cincinnati, Ohio, 45236
TG Therapeutics Investigational Trial Site
Columbia, Maryland, 21044
TG Therapeutics Investigational Trial Site
Columbia, Missouri, 65212
TG Therapeutics Investigational Trial Site
Concord, California, 94520
TG Therapeutics Investigational Trial Site
Danville, Pennsylvania, 17822
TG Therapeutics Investigational Trial Site
Decatur, Illinois, 62526
TG Therapeutics Investigational Trial Site
Denver, Colorado, 80218
TG Therapeutics Investigational Trial Site
Detroit, Michigan, 48202
TG Therapeutics Investigational Trial Site
Duarte, California, 91010
TG Therapeutics Investigational Trial Site
Durham, North Carolina, 27710
TG Therapeutics Investigational Trial Site
Durham, North Carolina
TG Therapeutics Investigational Trial Site
East Setauket, New York, 11733
TG Therapeutics Investigational Trial Site
Fayetteville, Arkansas, 72703
TG Therapeutics Investigational Trial Site
Fort Belvoir, Virginia, 22060
TG Therapeutics Investigational Trial Site
Fort Myers, Florida, 33916
TG Therapeutics Investigational Trial Site
Fort Wayne, Indiana, 46804
TG Therapeutics Investigational Trial Site
Fort Worth, Texas, 76104
TG Therapeutics Investigational Trial Site
Glens Falls, New York, 12801
TG Therapeutics Investigational Trial Site
Greenbrae, California, 94904
TG Therapeutics Investigational Trial Site
Greenville, South Carolina, 29615
TG Therapeutics Investigational Trial Site
Hershey, Pennsylvania, 17033
TG Therapeutics Investigational Trial Site
Hickory, North Carolina, 28602
TG Therapeutics Investigational Trial Site
Houston, Texas, 77030
TG Therapeutics Investigational Trial Site
Huntsville, Alabama, 35805
TG Therapeutics Investigational Trial Site
Indianapolis, Indiana, 46237
TG Therapeutics Investigational Trial Site
Jackson, Michigan, 49201
TG Therapeutics Investigational Trial Site
Jacksonville, Florida, 32204
TG Therapeutics Investigational Trial Site
Jacksonville, Florida, 32256
TG Therapeutics Investigational Trial Site
Kansas City, Kansas, 64132
TG Therapeutics Investigational Trial Site
Kansas City, Missouri
TG Therapeutics Investigational Trial Site
Kinston, North Carolina, 28501
TG Therapeutics Investigational Trial Site
Las Vegas, Nevada, 89119
TG Therapeutics Investigational Trial Site
Lebanon, New Hampshire, 03756
TG Therapeutics Investigational Trial Site
Lincoln, Nebraska, 68510
TG Therapeutics Investigational Trial Site
Louisville, Kentucky, 40207
TG Therapeutics Investigational Trial Site
Macon, Georgia, 31201
TG Therapeutics Investigational Trial Site
Maywood, Illinois, 60153
TG Therapeutics Investigational Trial Site
Milwaukee, Wisconsin, 53226
TG Therapeutics Investigational Trial Site
Mobile, Alabama, 36604
TG Therapeutics Investigational Trial Site
Morristown, New Jersey, 07962
TG Therapeutics Investigational Trial Site
Nashville, Tennessee, 37203
TG Therapeutics Investigational Trial Site
New Haven, Connecticut, 06519
TG Therapeutics Investigational Trial Site
Newark, Delaware, 19713
TG Therapeutics Investigational Trial Site
Niles, Illinois, 60714
TG Therapeutics Investigational Trial Site
Ocala, Florida, 34471
TG Therapeutics Investigational Trial Site
Ogden, Utah, 84405
TG Therapeutics Investigational Trial Site
Olympia, Washington, 98502
TG Therapeutics Investigational Trial Site
Pawtucket, Rhode Island, 00286
TG Therapeutics Investigational Trial Site
Pensacola, Florida, 32504
TG Therapeutics Investigational Trial Site
Peoria, Illinois, 61615
TG Therapeutics Investigational Trial Site
Philadelphia, Pennsylvania, 19106
TG Therapeutics Investigational Trial Site
Phoenix, Arizona, 85016
TG Therapeutics Investigational Trial Site
Pismo Beach, California, 93449
TG Therapeutics Investigational Trial Site
Pittsburgh, Pennsylvania, 15224
TG Therapeutics Investigational Trial Site
Pittsburgh, Pennsylvania, 15232
TG Therapeutics Investigational Trial Site
Pleasanton, California, 94588
TG Therapeutics Investigational Trial Site
Portland, Oregon, 97227
TG Therapeutics Investigational Trial Site
Portland, Oregon, 97239
TG Therapeutics Investigational Trial Site
Raleigh, North Carolina, 27607
TG Therapeutics Investigational Trial Site
Saint Louis Park, Minnesota, 55416
TG Therapeutics Investigational Trial Site
San Antonio, Texas, 78217
TG Therapeutics Investigational Trial Site
San Antonio, Texas, 78229
TG Therapeutics Investigational Trial Site
San Diego, California, 92120
TG Therapeutics Investigational Trial Site
Santa Barbara, California, 93105
TG Therapeutics Investigational Trial Site
Seattle, Washington, 98104
TG Therapeutics Investigational Trial Site
Seattle, Washington, 98109
TG Therapeutics Investigational Trial Site
Sioux Falls, South Dakota, 57105
TG Therapeutics Investigational Trial Site
Somerville, New Jersey, 00876
TG Therapeutics Investigational Trial Site
Spokane, Washington, 99216
TG Therapeutics Investigational Trial Site
Springfield, Oregon, 97477
TG Therapeutics Investigational Trial Site
St. Petersburg, Florida, 33705
TG Therapeutics Investigational Trial Site
Stamford, Connecticut, 06904
TG Therapeutics Investigational Trial Site
Swansea, Illinois
TG Therapeutics Investigational Trial Site
Syracuse, New York, 13210
TG Therapeutics Investigational Trial Site
Tallahassee, Florida, 32308
TG Therapeutics Investigational Trial Site
Tampa, Florida, 33612
TG Therapeutics Investigational Trial Site
Toledo, Ohio, 43623
TG Therapeutics Investigational Trial Site
Tucson, Arizona, 85711
TG Therapeutics Investigational Trial Site
Tyler, Texas, 75702
TG Therapeutics Investigational Trial Site
Urbana, Illinois, 61801
TG Therapeutics Investigational Trial Site
Vancouver, Washington, 98684
TG Therapeutics Investigational Trial Site
Washington, North Carolina, 27889
TG Therapeutics Investigational Trial Site
Watertown, South Dakota, 57201
TG Therapeutics Investigational Trial Site
Wauwatosa, Wisconsin, 53226
TG Therapeutics Investigational Trial Site
West Palm Beach, Florida, 33407
TG Therapeutics Investigational Trial Site
Westwood, Kansas, 66210
TG Therapeutics Investigational Trial Site
Whittier, California, 90603
TG Therapeutics Investigational Trial Site
Worcester, Massachusetts, 01608
TG Therapeutics Investigational Trial Site
Yakima, Washington, 98902

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United Kingdom12 sites

TG Therapeutics Investigational Trial Site
Cambridge
TG Therapeutics Investigational Trial Site
Cumbria
TG Therapeutics Investigational Trial Site
Dudley West
TG Therapeutics Investigational Trial Site
London
TG Therapeutics Investigational Trial Site
Northbrook
TG Therapeutics Investigational Trial Site
Northumbria
TG Therapeutics Investigational Trial Site
Norwich
TG Therapeutics Investigational Trial Site
Peterborough
TG Therapeutics Investigational Trial Site
Southampton
TG Therapeutics Investigational Trial Site
St. James
TG Therapeutics Investigational Trial Site
Sunderland
TG Therapeutics Investigational Trial Site
Wolverhampton

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Russia9 sites

TG Therapeutics Investigational Trial Site
Krasnozatonskiy
TG Therapeutics Investigational Trial Site
Moscow
TG Therapeutics Investigational Trial Site
Perm
TG Therapeutics Investigational Trial Site
Petrozavodsk
TG Therapeutics Investigational Trial Site
Rodionova
TG Therapeutics Investigational Trial Site
Saint Petersburg
TG Therapeutics Investigational Trial Site
Smolensk
TG Therapeutics Investigational Trial Site
Tula
TG Therapeutics Investigational Trial Site
Yaroslavl

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Poland8 sites

TG Therapeutics Investigational Trial Site
Chorzów
TG Therapeutics Investigational Trial Site
Gdynia
TG Therapeutics Investigational Trial Site
Krakow
TG Therapeutics Investigational Trial Site
Lodz
TG Therapeutics Investigational Trial Site
Lublin
TG Therapeutics Investigational Trial Site
Słupsk
TG Therapeutics Investigational Trial Site
Warsaw
TG Therapeutics Investigational Trial Site
Wroclaw

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Israel7 sites

TG Therapeutics Investigational Trial Site
Ashkelon
TG Therapeutics Investigational Trial Site
Beersheba
TG Therapeutics Investigational Trial Site
Haifa
TG Therapeutics Investigational Trial Site
Jerusalem
TG Therapeutics Investigational Trial Site
Nahariya
TG Therapeutics Investigational Trial Site
Petah Tikva
TG Therapeutics Investigational Trial Site
Tel Aviv

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Italy5 sites

TG Therapeutics Investigational Trial Site
Bologna
TG Therapeutics Investigational Trial Site
Ferrara
TG Therapeutics Investigational Trial Site
Milan
TG Therapeutics Investigational Trial Site
Rome
TG Therapeutics Investigational Trial Site
Torino

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Spain3 sites

TG Therapeutics Investigational Trial Site
Barcelona
TG Therapeutics Investigational Trial Site
Madrid
TG Therapeutics Investigational Trial Site
Valencia

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About this study

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)

Conditions: Chronic Lymphocytic Leukemia
Being tested: Obinutuzumab, Ublituximab, TGR-1202, Chlorambucil
Medical subject headings: Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ObinutuzumabBiological
Also called GAZYVA
Obinutuzumab: IV infusion
UblituximabBiological
Ublituximab: IV infusion
TGR-1202Drug
TGR-1202: Oral daily dose
ChlorambucilDrug
Also called Leukeran
Chlorambucil: Oral dose

Study groups in NCT02612311
Study group	Role	What they receive
Arm A: Ublituximab + Umbralisib	Experimental	Participants received ublituximab, 150 milligrams (mg), intravenously (IV), on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 cycles thereafter, along with umbralisib, 800 mg, orally, once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months. Receives: Biological: Ublituximab; Drug: TGR-1202
Arm B: Obinutuzumab + Chlorambucil	Active comparator	Participants received Obinutuzumab 100 mg, IV on Day 1, 900 mg on Day 2, followed by 1000 mg on Days 8 and 15 of cycle 1 (cycle length = 28 days), Day 1 of Cycle 2-6 along with Chlorambucil 0.5 milligram per kilogram (mg/kg) tablet orally on Days 1 and 15 once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months. Receives: Biological: Obinutuzumab; Drug: Chlorambucil
Arm C: Ublituximab	Experimental	Participants received ublituximab, 150 mg, IV, on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 cycles thereafter, until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months. Receives: Biological: Ublituximab
Arm D: Umbralisib	Experimental	Participants received umbralisib, 800 mg tablets, orally, once daily during each cycle (cycle length= 28 days) until removal from study or up to 87 months. Receives: Drug: TGR-1202

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: From enrolment to the earlier of the first documentation of definitive disease progression (PD) or death (Up to 87 months)

Secondary outcomes (5)

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.
Measured: Up to 87 months
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.
Measured: Up to 87 months
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.
Measured: From Cycle 6 until Cycle 15 (cycle length=28 days) up to approximately 81.5 months
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.
Measured: From first documentation of response to study treatment till disease progression/death (up to approximately 87 months)
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.
Measured: From first dose of study treatment up to end of study (up to approximately 87 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Nov 201522 Feb 2023

First posted23 Nov 2015 (estimated)
Study start19 Nov 2015
Primary completion22 Feb 2023
Study completion22 Feb 2023

Why it stopped: Strategic/Business decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
More trials run by TG Therapeutics, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 603 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02612311
Sponsor's protocol ID: UTX-TGR-304
Other IDs: 2015-005758-36, 2015
Acronym: UNITY-CLL
Status last verified: Nov 2024
First submitted: 18 Nov 2015
Last updated: 13 Dec 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
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Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic

All Chronic Lymphocytic Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT02612311
Acronym / sponsor ID: UNITY-CLL / UTX-TGR-304
Conditions: Chronic Lymphocytic Leukemia
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Strategic/Business decision
Enrolment: 603 participants (actual)
Lead sponsor: TG Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 19 Nov 2015 (actual)
Primary completion: 22 Feb 2023 (actual)
Study completion: 22 Feb 2023 (actual)
First posted: 23 Nov 2015 (estimated)
Results: Posted 7 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Arm A: Ublituximab + Umbralisib	Experimental	Biological: Ublituximab, Drug: TGR-1202Participants received ublituximab, 150 milligrams (mg), intravenously (IV), on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 cycles thereafter, along with umbralisib, 800 mg, orally, once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
Arm B: Obinutuzumab + Chlorambucil	Active comparator	Biological: Obinutuzumab, Drug: ChlorambucilParticipants received Obinutuzumab 100 mg, IV on Day 1, 900 mg on Day 2, followed by 1000 mg on Days 8 and 15 of cycle 1 (cycle length = 28 days), Day 1 of Cycle 2-6 along with Chlorambucil 0.5 milligram per kilogram (mg/kg) tablet orally on Days 1 and 15 once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
Arm C: Ublituximab	Experimental	Biological: UblituximabParticipants received ublituximab, 150 mg, IV, on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 cycles thereafter, until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
Arm D: Umbralisib	Experimental	Drug: TGR-1202Participants received umbralisib, 800 mg tablets, orally, once daily during each cycle (cycle length= 28 days) until removal from study or up to 87 months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Treatment naïve or previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
Eastern Cooperative Oncology Group (ECOG) score of 0 to 2

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ObinutuzumabAlso: GAZYVAObinutuzumab: IV infusion	Biological	Arm B: Obinutuzumab + Chlorambucil
UblituximabUblituximab: IV infusion	Biological	Arm A: Ublituximab + Umbralisib, Arm C: Ublituximab
TGR-1202TGR-1202: Oral daily dose	Drug	Arm A: Ublituximab + Umbralisib, Arm D: Umbralisib
ChlorambucilAlso: LeukeranChlorambucil: Oral dose	Drug	Arm B: Obinutuzumab + Chlorambucil

Primary outcome

Progression-Free Survival (PFS) Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria
Time frame: From enrolment to the earlier of the first documentation of definitive disease progression (PD) or death (Up to 87 months)
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).

5 secondary outcomes

Overall Response Rate (ORR) Per iwCLL Criteria
Time frame: Up to 87 months
Complete Response (CR) Rate
Time frame: Up to 87 months
Minimal Residual Disease (MRD) Negativity Rate
Time frame: From Cycle 6 until Cycle 15 (cycle length=28 days) up to approximately 81.5 months
Duration of Response (DOR)
Time frame: From first documentation of response to study treatment till disease progression/death (up to approximately 87 months)
Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: From first dose of study treatment up to end of study (up to approximately 87 months)

Results and safety

Results posted to the registry on 7 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Experimental: Arm A: Ublituximab + Umbralisib	210	0
Active Comparator: Arm B: Obinutuzumab + Chlorambucil	211	0
Experimental: Arm C: Ublituximab	91	0
Experimental: Arm D: Umbralisib	91	0

Primary outcome: Progression-Free Survival (PFS) Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria

Time frame: From enrolment to the earlier of the first documentation of definitive disease progression (PD) or death (Up to 87 months). Median (95% Confidence Interval). Unit: Months

Measure	Experimental: Arm A: Ublituximab + Umbralisib n = 210	Active Comparator: Arm B: Obinutuzumab + Chlorambucil n = 211	Experimental: Arm C: Ublituximab n = 91	Experimental: Arm D: Umbralisib n = 91
Value	33.2 (27.7 to 39.6)	17.5 (16.6 to 22.6)	32.9 (19.1 to 45.0)	22.4 (17.2 to 34.7)

Population analysed: The ITT population included all randomized participants, regardless of administration of study treatment (ublituximab, TGR-1202, obinutuzumab + chlorambucil, or ublituximab + TGR-1202).

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study treatment up to end of study (up to approximately 87 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Experimental: Arm A: Ublituximab + Umbralisib	118 of 206 (57.3%)	205 of 206 (99.5%)	82 of 206
Active Comparator: Arm B: Obinutuzumab + Chlorambucil	47 of 200 (23.5%)	189 of 200 (94.5%)	40 of 200
Experimental: Arm C: Ublituximab	33 of 91 (36.3%)	84 of 91 (92.3%)	25 of 91
Experimental: Arm D: Umbralisib	34 of 86 (39.5%)	84 of 86 (97.7%)	29 of 86

Limitations and caveats (from the sponsor): Due to sponsor's business decision, the clinical trial was terminated by the sponsor prematurely. As such, the study results are reflective of the data captured to the time of study termination and with limited data verification.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

154 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Obinutuzumab, Ublituximab and TGR-1202 in people with Chronic Lymphocytic Leukemia, run by TG Therapeutics, Inc. at 154 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 154 sites in United States, United Kingdom, Russia, Poland, Israel and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria (time frame: From enrolment to the earlier of the first documentation of definitive disease progression (PD) or death (Up to 87 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02612311.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.