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NCT04149821

Umbralisib Plus Ublituximab (U2) in Progressive CLL After Novel Therapy

Terminated Phase 2 Results posted Last updated 15 June 2023
What this trial tests

Phase 2 trial testing Umbralisib in Chronic Lymphocytic Leukemia in 1 participant. Terminated before completion.

Timeline
10 February 2021
Primary endpoint
21 January 2022
9 June 2022

Quick facts

Lead sponsorWeill Medical College of Cornell University
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment1
Start date10 February 2021
Primary completion21 January 2022
Estimated completion9 June 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Weill Medical College of Cornell University

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia or CLL Progression. 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.

Efficacy of Umbralisib in Combination With Ublituximab (U2) as Measured by Overall Response Rate (ORR) in Patients With CLL Who Have Progressed on a BTKi or BCL-2 Inhibitor Primary · 11 months

Number of subjects who achieve a partial or complete response

GroupValue95% CI
Cohort B Post BCL-2 Therapy0
Safety of Umbralisib in Combination With Ublituximab (U2) as Measured by the Percentage of Subjects Who Experience 1 or More Adverse Events Secondary · 1 year and 4 months

Rate of subjects who experience 1 or more adverse events

GroupValue95% CI
Cohort B Post BCL-2 Therapy1
Complete Remission Rate as Measured by the Number of Subjects Who Achieve Complete Response as Their Best Response Secondary · 1 year and 4 months

Number of subjects who achieve complete response on study

GroupValue95% CI
Cohort B Post BCL-2 Therapy0
Duration of Response Secondary · 1 year and 4 months

Median interval of time between subjects' first objective response to the first sign of disease progression

GroupValue95% CI
Cohort B Post BCL-2 Therapy0

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year and 3 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A Post BTKi Therapy
Serious: 0
Deaths: 0
Cohort B Post BCL-2 Therapy
Serious: 1/1 (100%)
Deaths: 0/1

Serious adverse events (3 terms)

ReactionSystemCohort A Post BTKi TherapyCohort B Post BCL-2 Therapy
VomitingGastrointestinal disorders
HyponatremiaMetabolism and nutrition disorders
SyncopeNervous system disorders
Other adverse events (22 terms — click to expand)

ReactionSystemCohort A Post BTKi TherapyCohort B Post BCL-2 Therapy
Blurred visionEye disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
FatigueGeneral disorders
Lactate dehydrogenase increasedInvestigations
AnemiaBlood and lymphatic system disorders
HypocalcemiaInvestigations
Creatinine increasedInvestigations
ThrombocytopeniaInvestigations
DysuriaHepatobiliary disorders
DehydrationMetabolism and nutrition disorders
Tongue numbnessGeneral disorders
DyspneaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
NumbnessGeneral disorders
NeuropathyNervous system disorders
Axillary LymphadenopathyGeneral disorders
Abdominal PainGeneral disorders
ConstipationMetabolism and nutrition disorders
InsomniaPsychiatric disorders
Mouth SoresSkin and subcutaneous tissue disorders

Most-reported serious reactions: Vomiting, Hyponatremia, Syncope.

Data from ClinicalTrials.gov NCT04149821 adverse events section.

Sponsor's own description

This study evaluates the efficacy and safety of umbralisib and ublituximab (U2) as salvage therapy in patients with chronic lymphocytic leukemia (CLL) who have progressed either on a BTK inhibitor (BTKi) or BCL-2 inhibitor. The study will evaluate this combination in two parallel cohorts and subjects will be assigned based on which class of novel agent-containing regimen was used prior. Cohort A will consist of patients who progress after BTKi containing regimens and Cohort B will consist of patients who progress after a BCL-2 containing regimen. Subjects who progress on a regimen containing both a BTKi and a BCL-2 inhibitor, will be enrolled in cohort B. Each cohort will be evaluated independently of each other.

Publications & conference data

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

  1. Targeting Bruton's Tyrosine Kinase in CLL.
    Ahn IE, Brown JR. · · 2021 · cited 62× · PMID 34248972 · DOI 10.3389/fimmu.2021.687458
  2. Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies.
    van der Horst HJ, Nijhof IS, Mutis T, Chamuleau MED. · · 2020 · cited 56× · PMID 33086644 · DOI 10.3390/cancers12103041
  3. Overcoming resistance to targeted therapies in chronic lymphocytic leukemia.
    Skånland SS, Mato AR. · · 2021 · cited 42× · PMID 33570649 · DOI 10.1182/bloodadvances.2020003423
  4. PI3K Inhibitors for the Treatment of Chronic Lymphocytic Leukemia: Current Status and Future Perspectives.
    Hus I, Puła B, Robak T. · · 2022 · cited 34× · PMID 35326722 · DOI 10.3390/cancers14061571
  5. 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
  6. 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 Chronic Lymphocytic Leukemia

Currently open trials in the same condition.

Other Weill Medical College of Cornell University 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/NCT04149821.

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