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Chronic Lymphocytic LeukemiaPhase 3GENUINENCT02301156

Ublituximab in Combination With Ibrutinib Versus Ibrutinib Alone in Participants With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)

A Phase 3 study testing Ublituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia, run by TG Therapeutics, Inc. at 88 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study evaluates the effect of the addition of ublituximab, a novel monoclonal antibody, to ibrutinib compared to ibrutinib alone on antitumor activity, as measured by the overall response rate (ORR = CR [complete response] + PR [partial response]) in previously treated Chronic Lymphocytic Leukemia (CLL)… 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?
Ublituximab and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
126 participants
Where
88 sitesin 2 countries
Study dates
27 Jan 2015to 1 Apr 2020
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

  • Previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
  • At least one high-risk cytogenetic feature defined by the presence of 17p deletion, 11q deletion and/or p53 mutation
  • 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 human immunodeficiency virus (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)
  • Previous therapy with ibrutinib, or any drug that specifically inhibits Bruton's tyrosine kinase (BTK)

Trial locations and contacts

88 sites in 2 countries.

88 sites in 2 countries

United States87 sites

  • TG Therapeutics Investigational Trial Site

    Albany, Georgia, 31701

  • TG Therapeutics Investigational Trial Site

    Ames, Iowa, 50010

  • 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

    Baton Rouge, Louisiana, 70816

  • 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

    Cincinnati, Ohio, 45242

  • TG Therapeutics Investigational Trial Site

    Cleveland, Ohio, 44106

  • TG Therapeutics Investigational Trial Site

    Columbia, Maryland, 21044

  • TG Therapeutics Investigational Trial Site

    Coon Rapids, Minnesota, 55433

  • TG Therapeutics Investigational Trial Site

    Dallas, Texas, 75230

  • TG Therapeutics Investigational Trial Site

    Denton, Texas, 76201

  • TG Therapeutics Investigational Trial Site

    Detroit, Michigan, 48202

  • TG Therapeutics Investigational Trial Site

    Durham, North Carolina, 27710

  • TG Therapeutics Investigational Trial Site

    East Brunswick, New Jersey, 08816

  • TG Therapeutics Investigational Trial Site

    Evanston, Illinois, 60201

  • TG Therapeutics Investigational Trial Site

    Fayetteville, Arkansas, 72703

  • TG Therapeutics Investigational Trial Site

    Fort Myers, Florida, 33905

  • TG Therapeutics Investigational Trial Site

    Fort Sam Houston, Texas, 78234

  • TG Therapeutics Investigational Trial Site

    Fort Wayne, Indiana, 46804

  • TG Therapeutics Investigational Trial Site

    Fullerton, California, 92835

  • TG Therapeutics Investigational Trial Site

    Greenbrae, California, 94904

  • TG Therapeutics Investigational Trial Site

    Greenville, South Carolina, 29607

  • TG Therapeutics Investigational Trial Site

    Greenville, South Carolina, 29615

  • TG Therapeutics Investigational Trial Site

    Howell Township, New Jersey, 07731

  • TG Therapeutics Investigational Trial Site

    Huntsville, Alabama, 35805

  • TG Therapeutics Investigational Trial Site

    Indianapolis, Indiana, 46237

  • TG Therapeutics Investigational Trial Site

    Jonesboro, Arkansas, 72401

  • TG Therapeutics Investigational Trial Site

    Lebanon, New Hampshire, 03756

  • TG Therapeutics Investigational Trial Site

    Lincoln, Nebraska, 68510

  • TG Therapeutics Investigational Trial Site

    Los Angeles, California, 90045

  • TG Therapeutics Investigational Trial Site

    Maywood, Illinois, 60153

  • TG Therapeutics Investigational Trial Site

    Memphis, Tennessee, 38120

  • 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 Orleans, Louisiana, 70121

  • TG Therapeutics Investigational Trial Site

    New York, New York, 10019

  • TG Therapeutics Investigational Trial Site

    Newark, Delaware, 19173

  • TG Therapeutics Investigational Trial Site

    Newnan, Georgia, 30265

  • TG Therapeutics Investigational Trial Site

    Niles, Illinois, 60714

  • TG Therapeutics Investigational Trial Site

    Ogden, Utah, 84403

  • TG Therapeutics Investigational Trial Site

    Omaha, Nebraska, 68130

  • TG Therapeutics Investigational Trial Site

    Orange City, Florida, 32763

  • TG Therapeutics Investigational Trial Site

    Pawtucket, Rhode Island, 02860

  • TG Therapeutics Investigational Trial Site

    Pensacola, Florida, 32504

  • TG Therapeutics Investigational Trial Site

    Philadelphia, Pennsylvania, 19104

  • TG Therapeutics Investigational Trial Site

    Pismo Beach, California, 93449

  • TG Therapeutics Investigational Trial Site

    Pleasanton, California, 94588

  • TG Therapeutics Investigational Trial Site

    Pompton Plains, New Jersey, 07444

  • TG Therapeutics Investigational Trial Site

    Portland, Oregon, 97213-2982

  • TG Therapeutics Investigational Trial Site

    Portland, Oregon, 97227

  • TG Therapeutics Investigational Trial Site

    Raleigh, North Carolina, 27607

  • TG Therapeutics Investigational Trial Site

    Richmond, Virginia, 23230

  • TG Therapeutics Investigational Trial Site

    Saint Louis Park, Minnesota, 55416

  • TG Therapeutics Investigational Trial Site

    Salisbury, Maryland, 21801

  • TG Therapeutics Investigational Trial Site

    San Antonio, Texas, 78229

  • TG Therapeutics Investigational Trial Site

    Santa Barbara, California, 93105

  • TG Therapeutics Investigational Trial Site

    Seattle, Washington, 98104

  • TG Therapeutics Investigational Trial Site

    Sioux Falls, South Dakota, 57105

  • TG Therapeutics Investigational Trial Site

    Somerville, New Jersey, 08876

  • TG Therapeutics Investigational Trial Site

    Spokane, Washington, 99216

  • TG Therapeutics Investigational Trial Site

    Springfield, Massachusetts, 01199

  • TG Therapeutics Investigational Trial Site

    Springfield, Oregon, 97477

  • TG Therapeutics Investigational Trial Site

    St. Petersburg, Florida, 33709

  • TG Therapeutics Investigational Trial Site

    Stamford, Connecticut, 06904

  • TG Therapeutics Investigational Trial Site

    Syracuse, New York, 13210

  • TG Therapeutics Investigational Trial Site

    Tucson, Arizona, 85710

  • TG Therapeutics Investigational Trial Site

    Tyler, Texas, 75702

  • TG Therapeutics Investigational Trial Site

    Urbana, Illinois, 61801

  • TG Therapeutics Investigational Trial Site

    Vancouver, Washington, 98683

  • TG Therapeutics Investigational Trial Site

    Watertown, South Dakota, 57201

  • TG Therapeutics Investigational Trial Site

    Webster, Texas, 77598-4420

  • TG Therapeutics Investigational Trial Site

    West Palm Beach, Florida, 33401

  • TG Therapeutics Investigational Trial Site

    Westwood, Kansas, 66205

  • TG Therapeutics Investigational Trial Site

    Worcester, Massachusetts, 01608

Other trials in United States

Israel1 site

  • TG Therapeutics Investigational Trial Site

    Ashkelon

Other trials in Israel

About this study

Official title: A Phase 3, Randomized, Study to Assess the Efficacy and Safety of Ublituximab in Combination With Ibrutinib Compared to Ibrutinib Alone, in Patients With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)

This study evaluates the effect of the addition of ublituximab, a novel monoclonal antibody, to ibrutinib compared to ibrutinib alone on antitumor activity, as measured by the overall response rate (ORR = CR [complete response] + PR [partial response]) in previously treated Chronic Lymphocytic Leukemia (CLL) participants with high-risk cytogenetic features. Half of the participants will receive ublituximab in combination with ibrutinib, while the other half will receive ibrutinib alone.

Being tested
Ublituximab, Ibrutinib
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.

  • UblituximabDrug

    Also called TG-1101

    Administered as an IV infusion

  • IbrutinibDrug

    Also called IMBRUVICA

    Administered orally

Study groups in NCT02301156
Study groupRoleWhat they receive
Ublituximab + IbrutinibExperimentalParticipants will receive ublituximab intravenous (IV) infusion, up to 150 milligrams (mg) once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 62 months along with ibrutinib 420 mg capsules, orally, once daily (QD) in each 28-day cycle for up to 62 months.
Receives: Drug: Ublituximab; Drug: Ibrutinib
IbrutinibActive comparatorParticipants will receive ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 62 months.
Receives: Drug: Ibrutinib

What is being measured

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

  1. Overall Response Rate (ORR)

    ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: No evidence of new disease; Absolute lymphocyte count(ALC)<4x10^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters(cm) in longest diameter(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; Absolute neutrophil count(ANC)>1.5x10^9/L,platelets≥100x10^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR criteria: 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(SPD) 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.

    Measured: Up to 62 months

Secondary outcomes (6)

  1. Complete Response (CR) Rate

    The CR rate was defined as the percentage of participants who achieved CR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and 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 >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L.

    Measured: Up to 62 months

  2. Minimum Residual Disease (MRD) Negativity Rate

    MRD negativity rate was defined as the percentage of participants who were MRD negative post-baseline. 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: Up to 62 months

  3. Progression-Free Survival (PFS)

    PFS was defined as the time from the date of randomization until the date of first documentation of definitive disease progression (PD) or date of death from any cause, whichever occurs first. PD requires at least one of the following: New nodes >1.5 cm in the 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 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 g/L decrease from the highest on-study Hgb.

    Measured: From the randomization until the first documentation of PD or death whichever occurs first or up to 62 months

  4. Duration of Response (DOR)

    DOR:Interval from first documentation of CR/PR to first documentation of PD or death from any cause.CR:ALC<4x10^9/L;Regression to normal of target nodal masses,nodal non-target disease,and no detectable non-nodal,non-target disease;Normal spleen,liver size;Morphologically negative bone marrow,No lymphoid nodules;ANC>1.5x10^9/L,Platelets≥100x10^9/L,Hgb≥110 g/L.PR:Response in 2 or more:ALC<4x10^9/L,>=50% drop from baseline in ALC or SPD of target nodal lesions,Hepatosplenomegaly,>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules;Response in 1 or more:ANC>1.5x10^9/L,Platelets>100x10^9/L,Hgb>110 g/L or >=50% increase over baseline in any.PD:Response in 1 or more:new nodes,Hepatosplenomegaly,unequivocal extra-nodal lesion;≥50% increase from nadir in SPD of target lesions or LD of node/extra-nodal mass or Splenic/Hepatic size,Unequivocal increase in non-target disease,More aggressive histology;Drop of >50% in platelets/>20g/L in Hgb from highest on-study count.

    Measured: From the first dose of study drug until the first documentation of PD or death whichever occurs first or up to 62 months

  5. Time to Response (TTR)

    TTR was defined as the interval from the randomization to the first documentation of CR or PR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and 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 >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L. PR criteria: No evidence of new disease; Response in 2 of following when abnormal at baseline: ALC<4 x 10^9/L or >=50% decrease from baseline in SPD of target nodal lesions; splenomegaly; hepatomegaly; >=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; and Response in 1 of the following: ANC>1.5 x 10^9/L, platelets>100 x 10^9/L, Hgb>110 g/L or >=50% increase over baseline in any of these.

    Measured: From the randomization up to 62 months

  6. Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)

    An adverse event (AE) is 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 the first dose up to 30 days after the last dose of study drug (up to 57.3 months)

Timeline

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

  1. First posted25 Nov 2014 (estimated)
  2. Study start27 Jan 2015
  3. Primary completion1 Apr 2020
  4. Study completion1 Apr 2020

Resources

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
126 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02301156
Sponsor's protocol ID
UTX-IB-301
Acronym
GENUINE
Status last verified
Apr 2022
First submitted
20 Nov 2014
Last updated
20 May 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
No: TG Therapeutics does not currently plan to share IPD.

Publications

  • Sharman JP, Brander DM, Mato AR, Ghosh N, Schuster SJ, Kambhampati S, Burke JM, Lansigan F, Schreeder MT, Lunin SD, Zweibach A, Shtivelband M, Travis PM, Chandler JC, Kolibaba KS, Sportelli P, Miskin HP, Weiss MS, Flinn IW. Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial. Lancet Haematol. 2021 Apr;8(4):e254-e266. doi: 10.1016/S2352-3026(20)30433-6. Epub 2021 Feb 22.

    PubMed 33631112

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ublituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia, run by TG Therapeutics, Inc. at 88 sites in 2 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 3 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: finished, as of the sponsor's last update on 20 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 88 sites in United States, Israel. 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 20 May 2022). 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?

Overall Response Rate (ORR) (time frame: Up to 62 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 NCT02301156, which also lists 1 linked publication.

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 20 May 2022.

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