NCT03801525|TerminatedPhase 2ResultsDMCFDA Drug

Study Stopped

Strategic/Business decision

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)

ULTRA-V

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)

TG Therapeutics, Inc.ClinicalTrials.gov

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1 other identifier

U2-VEN-207

Study Type

interventional

Target

277

Locations

1 country

Sites

Timeline

RegisteredJan 2019

StartedMay 2019

CompletionDec 2022

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)

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

277

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started May 2019

Typical duration for phase_2

Geographic Reach

1 country

50 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.6 years study duration

First Submitted

Initial submission to the registry

January 9, 2019

Completed

2 days until next milestone

First Posted

Study publicly available on registry

January 11, 2019

Completed

4 months until next milestone

Study Start

First participant enrolled

May 16, 2019

Completed

3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 20, 2022

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 20, 2022

Completed

1.3 years until next milestone

Results Posted

Study results publicly available

April 19, 2024

Completed

Last Updated

April 19, 2024

Status Verified

April 1, 2024

Enrollment Period

3.6 years

First QC Date

January 9, 2019

Results QC Date

March 4, 2024

Last Update Submit

April 10, 2024

Conditions

Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma

Keywords

CLLSLL

Outcome Measures

Primary Outcomes (3)

Phase 2: Complete Response (CR) Rate as Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Criteria
CR rate=percent of participants who achieved CR or complete response with incomplete marrow recovery(CRi).CR=no evidence of new disease,absolute lymphocyte count(ALC) in peripheral blood\<4x10\^9 per liter(/L),regression of nodal masses to normal size \<1.5 centimeters(cm) in longest diameter(LD),normal spleen and liver size,no constitutional symptoms,cytological/pathological evaluation of bone marrow(BM) smear/biopsy must be at least normocellular for age without evidence for typical chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma(SLL) lymphocytes by morphological criteria,peripheral blood counts with absolute neutrophil count(ANC)≥1.5x10\^9/L or platelet≥100x10\^9/L or hemoglobin≥110 grams per liter(g/L) without red blood cell(RBC) transfusions,all without need for exogenous growth factors.CRi=all CR criteria but with persistent anemia,thrombocytopenia,or neutropenia or hypocellular BM that is related to prior/ongoing drug toxicity(and not to CLL/SLL).
Up to 43.2 months
Phase 2: Overall Response Rate (ORR) Per iwCLL 2018 Criteria
ORR=percent of participants who achieve CR,CRi,partial response(PR) or PR with lymphocytosis(PR-L).CR=no evidence of new disease;ALC\<4x10\^9/L;regression of nodal masses to\<1.5cm LD;normal spleen,liver size;no constitutional symptoms;cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age;ANC≥1.5x10\^9/L,platelet≥100x10\^9/L,Hb≥110g/L.CRi=CR criteria but with persistent anemia,thrombocytopenia,or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from baseline(BL) in ALC(or decrease to\<4x10\^9/L) or sum of products(SPD) of target nodal lesions or CLL/SLL marrow infiltrate/Blymphoid;no target,splenic,liver,or non-target disease with worsening that meets criteria for definitive progressive disease(PD);platelet\>100x10\^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to\<4x10\^9/L.
Up to 43.2 months
Phase 3: Progression-Free Survival (PFS) Per iwCLL 2018 Criteria
PFS was assessed in participants treated with U2-V compared with U2. PFS was defined as the interval between randomization and the date of definitive PD (as confirmed by the IRC) or death due to any cause, whichever occurs first. Participants who had no event (progression or death) were censored at the day of their last adequate disease assessment. PD= appearance of new nodes \>1.5 cm in the LD, \>50% increase in greatest diameter, new or recurrent hepatomegaly or splenomegaly, new unequivocal extra-nodal lesion, new non-target disease, ≥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 g/L decrease from the highest on-study Hgb.
Up to 43.2 months

Secondary Outcomes (7)

Minimal Residual Disease (MRD) Negativity Rate
Up to 43.2 months
Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)
Up to 43.2 months
Phase 2: Time to Response (TTR) Per iwCLL 2018 Criteria
Up to 43.2 months
Phase 2: Duration of Response (DOR) Per iwCLL 2018 Criteria
Up to 43.2 months
Phase 3: CR Rate as Assessed by an Independent Review Committee (IRC) Per iwCLL 2018 Criteria
Up to 43.2 months
+2 more secondary outcomes

Study Arms (3)

Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V)

EXPERIMENTAL

Participants were administered ublituximab, 150 milligrams (mg), intravenous (IV) infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6; umbralisib, 800 mg, oral tablet, once daily (QD) through Cycles 1-24; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-24. MRD positive participants were administered umbralisib, 800 mg, oral tablet, QD, on Days 1-28 from Cycle 25 onwards (1 Cycle = 28 days), until disease progression, unacceptable toxicity, or withdrawal from the study.

Drug: UblituximabDrug: UmbralisibDrug: Venetoclax

Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V)

EXPERIMENTAL

Participants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, 9,12, and 15; umbralisib, 800 mg, oral tablet, QD through Cycles 1-15; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-15 (1 Cycle = 28 days).

Drug: UblituximabDrug: UmbralisibDrug: Venetoclax

Phase 3: Ublituximab + Umbralisib (U2)

EXPERIMENTAL

Participants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, then every three cycles along with umbralisib, 800 mg, oral tablet, QD (1 Cycle = 28 days) from Cycle 1 until disease progression, unacceptable toxicity, or withdrawal from the study.

Drug: UblituximabDrug: Umbralisib

Interventions

UblituximabDRUG

* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody * administered as an IV infusion

Also known as: TG-1101

Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V)Phase 3: Ublituximab + Umbralisib (U2)Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V)

UmbralisibDRUG

* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) * Tablet form

Also known as: TGR-1202, UKONIQ

Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V)Phase 3: Ublituximab + Umbralisib (U2)Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V)

VenetoclaxDRUG

* B-cell lymphoma 2 (BCL-2) inhibitor * Tablet form

Also known as: Venclexta®

Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V)Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.