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NCT02301156: GENUINE

Ublituximab in Combination With Ibrutinib Versus Ibrutinib Alone in Participants With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)

Completed Phase 3 Results posted Last updated 20 May 2022
What this trial tests

Phase 3 trial testing Ublituximab in Chronic Lymphocytic Leukemia in 126 participants. Completed in 1 April 2020.

Timeline
27 January 2015
Primary endpoint
1 April 2020
1 April 2020

Quick facts

Lead sponsorTG Therapeutics, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment126
Start date27 January 2015
Primary completion1 April 2020
Estimated completion1 April 2020
Sites88 locations across United States, Israel

Drugs / interventions tested

Conditions studied

Sponsor

TG Therapeutics, Inc. — full company profile →

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia. 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) Primary · Up to 62 months

ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: 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)

GroupValue95% CI
Ublituximab + Ibrutinib84.4
Ibrutinib69.4
Complete Response (CR) Rate Secondary · Up to 62 months

The CR rate was defined as the percentage of participants who achieved CR. CR criteria: 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.

GroupValue95% CI
Ublituximab + Ibrutinib18.8
Ibrutinib4.8
Minimum Residual Disease (MRD) Negativity Rate Secondary · Up to 62 months

MRD negativity rate was defined as the percentage of participants who were MRD negative post-baseline. If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow.

GroupValue95% CI
Ublituximab + Ibrutinib45.332.8 – 58.3
Ibrutinib9.73.6 – 19.9
Progression-Free Survival (PFS) Secondary · From the randomization until the first documentation of PD or death whichever occurs first or up to 62 months

PFS was defined as the time from the date of randomization until the date of first documentation of definitive disease progression (PD) or date of death from any cause, whichever occurs first. PD requires at least one of the following: 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 target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from

GroupValue95% CI
Ublituximab + IbrutinibNANA – NA
Ibrutinib47.218.9 – NA
Duration of Response (DOR) Secondary · From the first dose of study drug until the first documentation of PD or death whichever occurs first or up to 62 months

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

GroupValue95% CI
Ublituximab + IbrutinibNANA – NA
Ibrutinib39.116.7 – NA
Time to Response (TTR) Secondary · From the randomization up to 62 months

TTR was defined as the interval from the randomization to the first documentation of CR or PR. CR criteria: 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. PR criteria: No evidence of new disease; Response in 2 of following when abnormal at baseline: ALC\<4

GroupValue95% CI
Ublituximab + Ibrutinib2.02.0 – 2.1
Ibrutinib3.92.2 – 8.3
Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE) Secondary · From the first dose up to 30 days after the last dose of study drug (up to 57.3 months)

An adverse event (AE) is 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. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subseque

GroupValue95% CI
Ublituximab + Ibrutinib100
Ibrutinib100

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events: From the first dose up to 30 days after the last dose of study drug (up to 57.3 months); All-Cause Mortality: From the first dose up to end of study (up to 62 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ublituximab + Ibrutinib
Serious: 38/59 (64%)
Deaths: 5/59
Ibrutinib
Serious: 31/58 (53%)
Deaths: 9/58

Serious adverse events (87 terms)

ReactionSystemUblituximab + IbrutinibIbrutinib
PneumoniaInfections and infestations
Atrial fibrillationCardiac disorders
Febrile neutropeniaBlood and lymphatic system disorders
SepsisInfections and infestations
Cardiac failureCardiac disorders
DiarrhoeaGastrointestinal disorders
DysphagiaGastrointestinal disorders
PyrexiaGeneral disorders
CellulitisInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skinNeoplasms benign, malignant and unspecified (incl cysts and polyps)
SyncopeNervous system disorders
Mental status changesPsychiatric disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Angina pectorisCardiac disorders
Atrial flutterCardiac disorders
Cardiac arrestCardiac disorders
Coronary artery diseaseCardiac disorders
PericarditisCardiac disorders
Acute myocardial infarctionCardiac disorders
Cardiac failure congestiveCardiac disorders
Other adverse events (128 terms — click to expand)

ReactionSystemUblituximab + IbrutinibIbrutinib
DiarrhoeaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Upper respiratory tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
AnaemiaBlood and lymphatic system disorders
PyrexiaGeneral disorders
ContusionInjury, poisoning and procedural complications
InsomniaPsychiatric disorders
Oedema peripheralGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
NeutropeniaBlood and lymphatic system disorders
ChillsGeneral disorders
SinusitisInfections and infestations
DizzinessNervous system disorders
ConstipationGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
DyspepsiaGastrointestinal disorders
StomatitisGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
PneumoniaInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Dry mouthGastrointestinal disorders
HypogammaglobulinaemiaImmune system disorders
Neutrophil count decreasedInvestigations
Productive coughRespiratory, thoracic and mediastinal disorders
Upper-airway cough syndromeRespiratory, thoracic and mediastinal disorders
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
Platelet count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Pneumonia, Atrial fibrillation, Febrile neutropenia, Sepsis, Cardiac failure, Diarrhoea, Dysphagia, Pyrexia.

Data from ClinicalTrials.gov NCT02301156 adverse events section.

Sponsor's own description

This study evaluates the effect of the addition of ublituximab, a novel monoclonal antibody, to ibrutinib compared to ibrutinib alone on antitumor activity, as measured by the overall response rate (ORR = CR \[complete response\] + PR \[partial response\]) in previously treated Chronic Lymphocytic Leukemia (CLL) participants with high-risk cytogenetic features. Half of the participants will receive ublituximab in combination with ibrutinib, while the other half will receive ibrutinib alone.

Publications & conference data

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

  1. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  2. Antibodies to watch in 2019.
    Kaplon H, Reichert JM. · · 2019 · cited 324× · PMID 30516432 · DOI 10.1080/19420862.2018.1556465
  3. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  4. Antibodies to watch in 2017.
    Reichert JM. · · 2017 · cited 194× · PMID 27960628 · DOI 10.1080/19420862.2016.1269580
  5. Antibodies to watch in 2018.
    Kaplon H, Reichert JM. · · 2018 · cited 179× · PMID 29300693 · DOI 10.1080/19420862.2018.1415671
  6. Therapeutic Antibodies: What Have We Learnt from Targeting CD20 and Where Are We Going?
    Marshall MJE, Stopforth RJ, Cragg MS. · · 2017 · cited 132× · PMID 29046676 · DOI 10.3389/fimmu.2017.01245
  7. BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.
    Alu A, Lei H, Han X, Wei Y, et al · · 2022 · cited 88× · PMID 36183125 · DOI 10.1186/s13045-022-01353-w
  8. Advances in targeted therapy for malignant lymphoma.
    Wang L, Qin W, Huo YJ, Li X, et al · · 2020 · cited 88× · PMID 32296035 · DOI 10.1038/s41392-020-0113-2

Verify or expand the search:

Other trials of Ublituximab

Trials testing the same drug.

Other recruiting trials for Chronic Lymphocytic Leukemia

Currently open trials in the same condition.

Other TG Therapeutics, Inc. trials

Trials by the same sponsor.

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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/NCT02301156.

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