NCT02656303|TerminatedPhase 2ResultsFDA Drug

Study Stopped

Strategic/Business Decision

A Study to Evaluate the Safety and Efficacy of Ublituximab in Combination With Umbralisib for Participants Previously Enrolled in Protocol UTX-TGR-304

A Multi-Center, Open-Label, Compassionate Use Extension Study of Ublituximab (TG-1101) in Combination With Umbralisib (TGR-1202) for Patients Previously Enrolled in Protocol UTX-TGR-304

TG Therapeutics, Inc.ClinicalTrials.gov

Compare

2 other identifiers

UTX-TGR-2042016-004339-19

Study Type

interventional

Target

116

Locations

4 countries

Sites

Timeline

RegisteredJan 2016

StartedJan 2016

CompletionJul 2022

Brief Summary

The purpose of this study was to provide the opportunity to the participants who progressed on treatment arm previously in the study UTX-TGR-304 (NCT02612311) to receive ublituximab (TG-1101) treatment in combination with umbralisib (TGR-1202).

Trial Health

Monitor

Trial Health Score

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

Enrollment

116

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Jan 2016

Longer than P75 for phase_2

Geographic Reach

4 countries

87 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

6.5 years study duration

Study Start

First participant enrolled

January 7, 2016

Completed

6 days until next milestone

First Submitted

Initial submission to the registry

January 13, 2016

Completed

1 day until next milestone

First Posted

Study publicly available on registry

January 14, 2016

Completed

6.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 26, 2022

Completed

2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 11, 2022

Completed

12 months until next milestone

Results Posted

Study results publicly available

June 22, 2023

Completed

Last Updated

June 22, 2023

Status Verified

May 1, 2023

Enrollment Period

6.4 years

First QC Date

January 13, 2016

Results QC Date

May 26, 2023

Last Update Submit

May 26, 2023

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (4)

Overall Response Rate (ORR) as Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria
ORR was defined as sum of participants with partial responses (PR) and complete responses (CR). CR: 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: 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.
Up to 76 months
Complete Response (CR) Rate Per iwCLL Criteria
The CR rate was defined as the percentage of participants who achieved CR. CR: 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.
Up to 76 months
Progression-Free Survival (PFS) Per 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 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 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 76 months
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.
Up to 76 months

Secondary Outcomes (2)

Minimal Residual Disease (MRD) Negativity Rate
From Cycle 6 until Cycle 15 (cycle length=28 days) (Up to approximately 76 months)
Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)
Up to 78 months

Study Arms (3)

Parent Study Arm B

EXPERIMENTAL

Participants from Arm B of the parent trial (UTX-TGR-304) 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 months 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 78 months.

Biological: UblituximabDrug: Umbralisib

Parent Study Arm C

EXPERIMENTAL

Participants from Arm C of the parent trial (UTX-TGR-304) received ublituximab, 900 mg, IV, on Day 1 of Cycles 1-6 (cycle length=28 days), and once every 3 months 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 78 months.

Biological: UblituximabDrug: Umbralisib

Parent Study Arm D

EXPERIMENTAL

Participants from Arm D of the parent trial (UTX-TGR-304) 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 months 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 78 months.

Biological: UblituximabDrug: Umbralisib

Interventions

UblituximabBIOLOGICAL

Ublituximab IV infusion

Also known as: TG-1101

Parent Study Arm BParent Study Arm CParent Study Arm D

UmbralisibDRUG

Umbralisib tablets

Also known as: TGR-1202

Parent Study Arm BParent Study Arm CParent Study Arm D

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

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

You may qualify if:

Prior treatment in clinical trial UTX-TGR-304
Eastern Cooperative Oncology Group (ECOG) score of 0 to 2

You may not qualify if:

Participants refractory to ublituximab + TGR-1202
Transformation of chronic lymphocytic leukemia (CLL) to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation)

Contact the study team to confirm eligibility.