Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)

Sponsor
TG Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03801525
Collaborator
(none)
700
Enrollment
50
Locations
7
Arms
71.5
Anticipated Duration (Months)
14
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

ULTRA-V: Study to Assess the Efficacy and Safety of Ublituximab in Combination with Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects with Chronic Lymphocytic Leukemia (CLL)

Detailed Description

This is an open-label, multicenter, Phase 2/3 study to evaluate the efficacy and safety of the combination of ublituximab + umbralisib + venetoclax (U2-V) compared to the combination of ublituximab + umbralisib (U2) in patients with either treatment naïve or previously treated CLL/ small lymphocytic lymphoma (SLL)

Study Design

Study Type:
Interventional
Anticipated Enrollment :
700 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2/3 Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects With Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date :
May 16, 2019
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
May 1, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Phase 2: Previously Treated CLL (BTK-Not Refractory)

Drug: Ublituximab
recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion
Other Names:
  • TG-1101
  • Drug: Umbralisib
    inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form
    Other Names:
  • TGR-1202
  • UKONIQ
  • Drug: Venetoclax
    B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally
    Other Names:
  • Venclexta®
  • Experimental: Phase 2: Previously Treated CLL (BTK-Refractory)

    Drug: Ublituximab
    recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion
    Other Names:
  • TG-1101
  • Drug: Umbralisib
    inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form
    Other Names:
  • TGR-1202
  • UKONIQ
  • Drug: Venetoclax
    B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally
    Other Names:
  • Venclexta®
  • Experimental: Phase 2: Treatment Naïve CLL

    Drug: Ublituximab
    recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion
    Other Names:
  • TG-1101
  • Drug: Umbralisib
    inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form
    Other Names:
  • TGR-1202
  • UKONIQ
  • Drug: Venetoclax
    B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally
    Other Names:
  • Venclexta®
  • Experimental: Phase 3: Treatment Naïve CLL/SLL: Ublituximab + Umbralisib + Venetoclax (U2-V)

    Drug: Ublituximab
    recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion
    Other Names:
  • TG-1101
  • Drug: Umbralisib
    inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form
    Other Names:
  • TGR-1202
  • UKONIQ
  • Drug: Venetoclax
    B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally
    Other Names:
  • Venclexta®
  • Experimental: Phase 3: Treatment Naïve CLL/SLL: Ublituximab + Umbralisib (U2)

    Drug: Ublituximab
    recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion
    Other Names:
  • TG-1101
  • Drug: Umbralisib
    inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form
    Other Names:
  • TGR-1202
  • UKONIQ
  • Experimental: Phase 3: Previously Treated CLL/SLL: Ublituximab + Umbralisib + Venetoclax (U2-V)

    Drug: Ublituximab
    recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion
    Other Names:
  • TG-1101
  • Drug: Umbralisib
    inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form
    Other Names:
  • TGR-1202
  • UKONIQ
  • Drug: Venetoclax
    B-cell lymphoma 2 (BCL-2) inhibitor Tablet form, to be taken orally
    Other Names:
  • Venclexta®
  • Experimental: Phase 3: Previously Treated CLL/SLL: Ublituximab + Umbralisib (U2)

    Drug: Ublituximab
    recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody administered as an intravenous (IV) infusion
    Other Names:
  • TG-1101
  • Drug: Umbralisib
    inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) Tablet form
    Other Names:
  • TGR-1202
  • UKONIQ
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 2: Complete Response (CR) Rate [Up to 12 months]

    2. Phase 2: Overall Response Rate [Up to 12 months]

    3. Phase 3: Progression-Free Survival [60 months]

      Progression-Free Survival in subjects treated with U2-V compared with U2

    Secondary Outcome Measures

    1. Adverse Events That Are Related to Treatment [6 months of therapy]

      Number of Participants With Treatment-Related Adverse Event and any potential abnormal laboratory results

    2. Phase 3: Overall Response Rate [Up to 12 months]

      Objective response in subjects treated with ublituximab + umbralisib + venetoclax

    3. Rate of Undetectable Minimal Residual Disease (MRD) [60 months]

    4. Phase 2: Time to Response (TTR) [Up to 12 months]

    5. Phase 2: Duration of Response (DOR) [60 months]

    6. Phase 3: Complete Response (CR) Rate [Up to 12 months]

    7. Phase 3: Overall Survival (OS) [72 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that warrants treatment

    • 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

    • Prior exposure to any PI3K inhibitor or venetoclax

    • Autologous hematologic stem cell transplant within 6 months of study entry. Prior allogeneic hematologic stem cell transplant is excluded

    • Active Hepatitis B or Hepatitis C.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1TG Therapeutics Investigational Trial SiteBirminghamAlabamaUnited States35294
    2TG Therapeutics Investigational Trial SiteHuntsvilleAlabamaUnited States35805
    3TG Therapeutics Investigational Trial SiteTucsonArizonaUnited States85711
    4TG Therapeutics Investigational Trial SiteDuarteCaliforniaUnited States91010
    5TG Therapeutics Investigational Trial SiteLa JollaCaliforniaUnited States92093
    6TG Therapeutics Investigational Trial SiteAuroraColoradoUnited States80012
    7TG Therapeutics Investigational Trial SiteStamfordConnecticutUnited States06904
    8TG Therapeutics Investigational Trial SiteBoca RatonFloridaUnited States33486
    9TG Therapeutics Investigational Trial SiteFort MyersFloridaUnited States33901
    10TG Therapeutics Investigational Trial SiteJacksonvilleFloridaUnited States32224
    11TG Therapeutics Investigational Trial SiteSaint PetersburgFloridaUnited States33705
    12TG Therapeutics Investigational Trial SiteTampaFloridaUnited States33612
    13TG Therapeutics Investigational Trial SiteAtlantaGeorgiaUnited States30322
    14TG Therapeutics Investigational Trial SiteDecaturIllinoisUnited States62526
    15TG Therapeutics Investigational Trial SiteNilesIllinoisUnited States60714
    16TG Therapeutics Investigational SitePeoriaIllinoisUnited States61615
    17TG Therapeutics Investigational Trial SiteFort WayneIndianaUnited States46804
    18TG Therapeutics Investigational Trial SiteIndianapolisIndianaUnited States46237
    19TG Therapeutics Investigational Trial SiteDes MoinesIowaUnited States50309
    20TG Therapeutics Investigational Trial SiteWestwoodKansasUnited States66210
    21TG Therapeutics Investigational SiteLouisvilleKentuckyUnited States40207
    22TG Therapeutics Investigational Trial SiteBethesdaMarylandUnited States37210
    23TG Therapeutics Investigational Trial SiteColumbiaMarylandUnited States21044
    24TG Therapeutics Investigational Trial SiteAnn ArborMichiganUnited States48197
    25TG Therapeutics Investigational Trial SiteDetroitMichiganUnited States48201
    26TG Therapeutics Investigational Trial SiteDetroitMichiganUnited States48202
    27TG Therapeutics Investigational Trial SiteRochesterMinnesotaUnited States55905
    28TG Therapeutics Investigational Trial SiteOmahaNebraskaUnited States68198
    29TG Therapeutics Investigational Trial SiteLebanonNew HampshireUnited States03756
    30TG Therapeutics Investigational Trial SiteHackensackNew JerseyUnited States07601
    31TG Therapeutics Investigational Trial SiteMorristownNew JerseyUnited States07960
    32TG Therapeutics Investigational Trial SiteNew YorkNew YorkUnited States10065
    33TG Therapeutics Investigational Trial SiteCharlotteNorth CarolinaUnited States28204
    34TG Therapeutics Investigational Trial SiteColumbusOhioUnited States43210
    35TG Therapeutics Investigational Trial SiteEugeneOregonUnited States97401
    36TG Therapeutics Investigational Trial SitePhiladelphiaPennsylvaniaUnited States19106
    37TG Therapeutics Investigational Trial SiteCharlestonSouth CarolinaUnited States29414
    38TG Therapeutics Investigational Trial SiteGreenvilleSouth CarolinaUnited States29616
    39TG Therapeutics Investigational Trial SiteChattanoogaTennesseeUnited States37404
    40TG Therapeutics Investigational Trial SiteKnoxvilleTennesseeUnited States37916
    41TG Therapeutics Investigational Trial SiteNashvilleTennesseeUnited States37203
    42TG Therapeutics Investigational Trial SiteAustinTexasUnited States78705
    43TG Therapeutics Investigational Trial SiteSan AntonioTexasUnited States78229
    44TG Therapeutics Investigational Trial SiteTylerTexasUnited States75702
    45TG Therapeutics Investigational Trial SiteOgdenUtahUnited States84405
    46TG Therapeutics Investigational Trial SiteSalt Lake CityUtahUnited States84106
    47TG Therapeutics Investigational Trial SiteBlacksburgVirginiaUnited States24060
    48TG Therapeutics Investigational Trial SiteGainesvilleVirginiaUnited States20155
    49TG Therapeutics Investigational Trial SiteSeattleWashingtonUnited States98104
    50TG Therapeutics Investigational Trial SiteSeattleWashingtonUnited States98108

    Sponsors and Collaborators

    • TG Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    TG Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT03801525
    Other Study ID Numbers:
    • U2-VEN-207
    First Posted:
    Jan 11, 2019
    Last Update Posted:
    Jan 13, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by TG Therapeutics, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 13, 2022