NCT02612311|TerminatedPhase 3ResultsDMCFDA Drug

Study Stopped

Strategic/Business decision

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

UNITY-CLL

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)

TG Therapeutics, Inc.ClinicalTrials.gov

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2 other identifiers

UTX-TGR-3042015-005758-36

Study Type

interventional

Target

603

Locations

7 countries

Sites

154

Timeline

RegisteredNov 2015

StartedNov 2015

CompletionFeb 2023

Brief 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.

Trial Health

Monitor

Trial Health Score

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

Enrollment

603

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Nov 2015

Longer than P75 for phase_3

Geographic Reach

7 countries

154 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

7.3 years study duration

First Submitted

Initial submission to the registry

November 18, 2015

Completed

1 day until next milestone

Study Start

First participant enrolled

November 19, 2015

Completed

4 days until next milestone

First Posted

Study publicly available on registry

November 23, 2015

Completed

7.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 22, 2023

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 22, 2023

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

May 7, 2024

Completed

Last Updated

December 13, 2024

Status Verified

November 1, 2024

Enrollment Period

7.3 years

First QC Date

November 18, 2015

Results QC Date

March 4, 2024

Last Update Submit

November 25, 2024

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

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 Outcomes (5)

Overall Response Rate (ORR) Per iwCLL Criteria
Up to 87 months
Complete Response (CR) Rate
Up to 87 months
Minimal Residual Disease (MRD) Negativity Rate
From Cycle 6 until Cycle 15 (cycle length=28 days) up to approximately 81.5 months
Duration of Response (DOR)
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)
From first dose of study treatment up to end of study (up to approximately 87 months)

Study Arms (4)

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.

Biological: UblituximabDrug: 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.

Biological: ObinutuzumabDrug: 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.

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.

Drug: TGR-1202

Interventions

ObinutuzumabBIOLOGICAL

Obinutuzumab: IV infusion

Also known as: GAZYVA

Arm B: Obinutuzumab + Chlorambucil

UblituximabBIOLOGICAL

Ublituximab: IV infusion

Arm A: Ublituximab + UmbralisibArm C: Ublituximab

TGR-1202DRUG

TGR-1202: Oral daily dose

Arm A: Ublituximab + UmbralisibArm D: Umbralisib

ChlorambucilDRUG

Chlorambucil: Oral dose

Also known as: Leukeran

Arm B: Obinutuzumab + Chlorambucil

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

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

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.