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NCT02939014

Brentuximab Vedotin in Chinese Participants With Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL)

Completed Phase 2 Results posted Last updated 24 February 2021
What this trial tests

Phase 2 trial testing Brentuximab Vedotin in Hodgkin Disease in 39 participants. Completed in 3 February 2020.

Timeline
7 November 2016
Primary endpoint
2 August 2018
3 February 2020

Quick facts

Lead sponsorTakeda
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment39
Start date7 November 2016
Primary completion2 August 2018
Estimated completion3 February 2020
Sites7 locations across China

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

18 and older, any sex, with Hodgkin Disease or Lymphoma, Large-Cell, Anaplastic. 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 · Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression death or end of treatment (approximately 12 months)

ORR is defined as the percentage of participants who have achieved complete remission (CR)=disappearance of all evidence of disease or partial remission (PR)=regression of greater than or equal to 50% of measurable disease and no new site by end of treatment (EOT) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.

GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)70.050.60 – 85.27
Brentuximab Vedotin 1.8 mg/kg (sALCL)66.729.93 – 92.51
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug.

GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)30
Brentuximab Vedotin 1.8 mg/kg (sALCL)9
Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events Primary · First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)

Clinical Laboratory tests included tests of Chemistry, Hematology and Urinalysis prespecified in the protocol. Abnormal laboratory values assessed by the investigator that lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be clinically significant changes from Baseline were recorded as Adverse Events. Neutropenia (pooled) includes preferred terms Neutropenia and Neutrophil count decreased.

Alanine aminotransferase increased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)18
Brentuximab Vedotin 1.8 mg/kg (sALCL)6
Aspartate aminotransferase increased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)17
Brentuximab Vedotin 1.8 mg/kg (sALCL)6
Gamma-glutamyltransferase increased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)3
Brentuximab Vedotin 1.8 mg/kg (sALCL)4
Blood bilirubin increased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)0
Brentuximab Vedotin 1.8 mg/kg (sALCL)2
Reticulocyte count decreased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)9
Brentuximab Vedotin 1.8 mg/kg (sALCL)2
Reticulocyte count increased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)6
Brentuximab Vedotin 1.8 mg/kg (sALCL)1
Haemoglobin decreased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)1
Brentuximab Vedotin 1.8 mg/kg (sALCL)1
Reticulocyte percentage increased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)1
Brentuximab Vedotin 1.8 mg/kg (sALCL)0
Number of Participants With Abnormal Vital Signs Reported as Adverse Events Primary · First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)

Vital signs included blood pressure in the sitting position, pulse rate, axillary temperature and weight. Abnormal vital sign values considered by the investigator to be clinically significant were recorded as Adverse Events.

Weight increased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)4
Brentuximab Vedotin 1.8 mg/kg (sALCL)2
Weight decreased
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)1
Brentuximab Vedotin 1.8 mg/kg (sALCL)2
Complete Remission (CR) Rate Secondary · Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment, and every 12 weeks during PFS follow-up period, until disease progression death or end of treatment (approximately 12 months)

CR rate is defined as the percentage of participants who have achieved CR by EOT. CR is defined as disappearance of all evidence of disease per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.

GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)20.07.71 – 38.57
Brentuximab Vedotin 1.8 mg/kg (sALCL)55.621.20 – 86.30
Duration of Response (DOR) Secondary · Up to 3.2 years

DOR is defined as the time between the first documentation of objective tumor response (CR or PR) and the first subsequent documentation of objective tumor progression or death due to any cause, whichever occurs first. CR is defined as disappearance of all evidence of disease. PR is defined as regression of greater than or equal to 50% of measurable disease and no new sites.

GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)12.04.37 – NA
Brentuximab Vedotin 1.8 mg/kg (sALCL)NA1.41 – NA
Progression Free Survival (PFS) Secondary · Up to 3.2 years

PFS is defined as the time from the start of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)13.56.77 – 17.81
Brentuximab Vedotin 1.8 mg/kg (sALCL)23.21.25 – NA
Overall Survival (OS) Secondary · Up to 3.2 years

Overall survival is defined as the time from the start of treatment to the date of death.

GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)NANA – NA
Brentuximab Vedotin 1.8 mg/kg (sALCL)NA3.19 – NA
B Symptom Resolution Rate Secondary · Day 1 of each cycle (each cycle was of 3 weeks) up to 30 days after last dose of study drug (approximately 12 months)

B Symptom Resolution Rate is defined as the percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss \>10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period.

GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg (HL)50.01.26 – 98.74
Brentuximab Vedotin 1.8 mg/kg (sALCL)100.0015.81 – 100.00
Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) Secondary · Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Cycle 1
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg36.9504± 9.90360
Cycle 2
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg32.4341± 5.83197
Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) Secondary · Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Cycle 1
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg38.2293± 7.95483
Cycle 2
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg39.9859± 12.43445
Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) Secondary · Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Cycle 1
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg5.1623± 3.69893
Cycle 2
GroupValue95% CI
Brentuximab Vedotin 1.8 mg/kg3.6218± 2.89331

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality: up to 3.2 years; Serious and Other Adverse Events: First dose of study drug up to 30 days post last dose of study drug (up to 12 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Brentuximab Vedotin 1.8 mg/kg (HL)
Serious: 1/30 (3%)
Deaths: 4/30
Brentuximab Vedotin 1.8 mg/kg (sALCL)
Serious: 1/9 (11%)
Deaths: 3/9

Serious adverse events (2 terms)

ReactionSystemBrentuximab Vedotin 1.8 mg…Brentuximab Vedotin 1.8 mg…
Large intestine polypGastrointestinal disorders
Lung infectionInfections and infestations
Other adverse events (99 terms — click to expand)

ReactionSystemBrentuximab Vedotin 1.8 mg…Brentuximab Vedotin 1.8 mg…
NeutropeniaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
LeukopeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
Reticulocyte count decreasedInvestigations
Peripheral sensory neuropathyNervous system disorders
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
Reticulocyte count increasedInvestigations
MalaiseGeneral disorders
PyrexiaGeneral disorders
Lymphocyte count decreasedInvestigations
DizzinessNervous system disorders
Gamma-glutamyltransferase increasedInvestigations
White blood cell count decreasedInvestigations
Weight increasedInvestigations
HypoaesthesiaNervous system disorders
VomitingGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
DyspepsiaGastrointestinal disorders
AstheniaGeneral disorders
HyperuricaemiaMetabolism and nutrition disorders
FlatulenceGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
PainGeneral disorders
RashSkin and subcutaneous tissue disorders
Night sweatsSkin and subcutaneous tissue disorders
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
Blood bilirubin increasedInvestigations
Total bile acids increasedInvestigations
Lymphocyte percentage decreasedInvestigations
Weight decreasedInvestigations
Platelet count decreasedInvestigations
Blood uric acid increasedInvestigations

Most-reported serious reactions: Large intestine polyp, Lung infection.

Data from ClinicalTrials.gov NCT02939014 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of brentuximab vedotin as a single agent in Chinese participants with relapsed/refractory CD30+ Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL).

Publications & conference data

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

  1. Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects.
    Tsuyama N, Sakamoto K, Sakata S, Dobashi A, et al · · 2017 · cited 79× · PMID 29279550 · DOI 10.3960/jslrt.17023
  2. Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current Standard and beyond.
    Prokoph N, Larose H, Lim MS, Burke GAA, et al · · 2018 · cited 58× · PMID 29601554 · DOI 10.3390/cancers10040099
  3. Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.
    Begalli F, Bennett J, Capece D, Verzella D, et al · · 2017 · cited 51× · PMID 28829404 · DOI 10.3390/biomedicines5030050
  4. The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target.
    Verzella D, Cornice J, Arboretto P, Vecchiotti D, et al · · 2022 · cited 23× · PMID 36140335 · DOI 10.3390/biomedicines10092233
  5. Phase II single-arm study of brentuximab vedotin in Chinese patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large cell lymphoma.
    Song Y, Guo Y, Huang H, Li W, et al · · 2021 · cited 18× · PMID 34275403 · DOI 10.1080/17474086.2021.1942831

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