Last reviewed · How we verify

NCT03364231

Study to Assess the Efficacy and Safety of Umbralisib in Participants With Non-Follicular Indolent Non-Hodgkin's Lymphoma

Completed Phase 2 Results posted Last updated 23 June 2023
What this trial tests

Phase 2 trial testing Umbralisib in Marginal Zone Lymphoma in 21 participants. Completed in 15 February 2022.

Timeline
30 November 2017
Primary endpoint
15 February 2022
15 February 2022

Quick facts

Lead sponsorTG Therapeutics, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment21
Start date30 November 2017
Primary completion15 February 2022
Estimated completion15 February 2022
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

TG Therapeutics, Inc. — full company profile →

Who can join

18 and older, any sex, with Marginal Zone Lymphoma or Waldenstrom Macroglobulinemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) as Assessed by Revised Response Criteria for Non- Hodgkin's Lymphoma (Lugano Classification) and Consensus-Based 6th International Workshop on Waldenstrom's Macroglobulinemia (IWWM) Primary · Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years

ORR for MZL=percentage of participants with complete response (CR)/partial response (PR). ORR for WM=CR/PR/very good partial response (VGPR)/minor response (MR). Response assessed per revised Lugano Classification for MZL \&per IWWM for WM participants. Per Lugano criteria CR=complete disappearance of all evidence of disease \& disease-related symptoms. PR=regression of measurable disease \& no new disease sites. Regression=≥50% decrease in the sum of the products of the diameters (SPD) of index lesions, with no increase in size of other lymph nodes/liver/spleen.Per IWWM criteria CR=disappeara

GroupValue95% CI
MZL: Umbralisib37.58.5 – 75.5
WM: Umbralisib30.06.7 – 65.2
Duration of Response (DOR) Primary · From the first demonstration of response to umbralisib till disease progression/death (up to approximately 4.2 years)

DOR is defined as the time from documentation of a response to treatment to the first documentation of tumor progression or death due to any cause, whichever comes first.

GroupValue95% CI
MZL: Umbralisib21.23 – 33
WM: Umbralisib135 – 14
Complete Response (CR) Rate Secondary · Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years

CR rate is defined as percentage of participants who achieved CR. CR was assessed using Revised Response Criteria for Non- Hodgkin's Lymphoma (Lugano Classification) for participants with MZL and Consensus-Based 6th IWWM for participants with WM. Per Lugano Classification, CR= the complete disappearance of all evidence of disease and disease-related symptoms i.e., liver/spleen non palpable and normal in size and disappearance of nodules related to lymphoma. Per IWWM criteria, CR=disappearance of serum monoclonal IgM protein by immunofixation with a normal serum IgM level, liver/spleen non pa

GroupValue95% CI
MZL: Umbralisib12.50.3 – 52.7
WM: Umbralisib0NA – NA
Progression-Free Survival (PFS) Secondary · From date of randomization until the date of first documented progression (up to approximately 4.2 years)

PFS is defined as the interval from Cycle 1 (1 cycle = 28 days) Day 1 to the earlier of the first documentation of definitive disease progression or death from any cause. Assessment of progressive disease (PD) was based on Revised Response Criteria for non-Hodgkin's lymphoma, Lugano Classification for participants with MZL and consensus-based 6th IWWM for participants with WM. Per Lugano Classification, PD was defined as the appearance of any new lesion more than 1.5 centimeters (cm) in any axis, even if other lesions are decreasing in size. At least a 50% increase from nadir in one of the fo

GroupValue95% CI
MZL: Umbralisib47.11.4 – 47.1
WM: Umbralisib18.42.1 – 35.0
Time to Treatment Failure (TTF) Secondary · From first dose on Day 1 of Cycle 1 (28 days = 1 cycle) up to discontinuation of treatment (up to approximately 4.2 years)

TTF is defined as a composite endpoint measuring time from Cycle 1/Day 1 to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. PD was assessed based on Revised Response Criteria for non-Hodgkin's lymphoma, Lugano Classification for participants with MZL and consensus-based 6th IWWM for participants with WM. Per Lugano Classification, PD was defined as the appearance of any new lesion more than 1.5 cm in any axis, even if other lesions are decreasing in size. At least a 50% increase from nadir in one of the following: SPD of index lesions

GroupValue95% CI
MZL: Umbralisib13.11.4 – NA
WM: Umbralisib6.52.1 – 15.9
Number of Participants With at Least One Adverse Event (AE) Secondary · From first dose of study treatment up to end of study (up to approximately 4.2 years)

An AE is any untoward medical occurrence in a participant that does not necessarily have to have a causal relationship with the treatment. An AE can therefore be 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.

GroupValue95% CI
MZL: Umbralisib8
WM: Umbralisib13

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study treatment up to end of study (up to approximately 4.2 years). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MZL: Umbralisib
Serious: 1/8 (13%)
Deaths: 1/8
WM: Umbralisib
Serious: 0/13 (0%)
Deaths: 0/13

Serious adverse events (1 terms)

ReactionSystemMZL: UmbralisibWM: Umbralisib
ColitisGastrointestinal disorders
Other adverse events (109 terms — click to expand)

ReactionSystemMZL: UmbralisibWM: Umbralisib
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
DizzinessNervous system disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
HeadacheNervous system disorders
PruritisSkin and subcutaneous tissue disorders
Night sweatsSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
PyrexiaGeneral disorders
AstheniaGeneral disorders
Influenza like illnessGeneral disorders
ContusionInjury, poisoning and procedural complications
Decreased apetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Upper airway cough syndromeRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Postnasal dripRespiratory, thoracic and mediastinal disorders
Upper respiratory infectionRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
HypertensionVascular disorders
LeukocytosisBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Mitral valve prolapseCardiac disorders
TachycardiaCardiac disorders
Otitis mediaEar and labyrinth disorders
TinnitusEar and labyrinth disorders

Most-reported serious reactions: Colitis.

Data from ClinicalTrials.gov NCT03364231 adverse events section.

Sponsor's own description

This research study will evaluate the safety and efficacy of a study drug called Umbralisib (also known as TGR-1202) alone as a possible treatment for Waldenstrom's Macroglobulinemia that has come back or that has not responded to standard treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
    Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
  2. Small molecule-based immunomodulators for cancer therapy.
    Wu Y, Yang Z, Cheng K, Bi H, et al · · 2022 · cited 71× · PMID 36562003 · DOI 10.1016/j.apsb.2022.11.007
  3. Immunometabolism in cancer: basic mechanisms and new targeting strategy.
    Su R, Shao Y, Huang M, Liu D, et al · · 2024 · cited 28× · PMID 38755125 · DOI 10.1038/s41420-024-02006-2
  4. Management of Waldenström macroglobulinemia in 2020.
    Castillo JJ, Treon SP. · · 2020 · cited 21× · PMID 33275726 · DOI 10.1182/hematology.2020000121
  5. Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.
    Pang Y, Lu T, Xu-Monette ZY, Young KH. · · 2023 · cited 16× · PMID 36982568 · DOI 10.3390/ijms24065493
  6. Integrated safety analysis of umbralisib, a dual PI3Kδ/CK1ε inhibitor, in relapsed/refractory lymphoid malignancies.
    Davids MS, O'Connor OA, Jurczak W, Samaniego F, et al · · 2021 · cited 16× · PMID 34547767 · DOI 10.1182/bloodadvances.2021005132
  7. Paediatric strategy forum for medicinal product development of PI3-K, mTOR, AKT and GSK3β inhibitors in children and adolescents with cancer.
    Pearson AD, DuBois SG, Macy ME, de Rojas T, et al · · 2024 · cited 10× · PMID 38936103 · DOI 10.1016/j.ejca.2024.114145
  8. WNT signaling in cancer: molecular mechanisms and potential therapies.
    Liang J, Pan Y, Yang J, Zeng D, et al · · 2025 · cited 2× · PMID 41120801 · DOI 10.1186/s43556-025-00327-x

Verify or expand the search:

Other trials of Umbralisib

Trials testing the same drug.

Other recruiting trials for Marginal Zone Lymphoma

Currently open trials in the same condition.

Other TG Therapeutics, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03364231.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing