Brentuximab Vedotin in Patients With Relapsed or Refractory EBV-and CD30-positive Lymphomas

Overview

This is an open-label, non-randomized, multi-center, phase II trial of brentuximab vedotin to evaluate ORR primarily in patients with EBV- and CD30-positive lymphomas.

Full Title of Study: “A Phase II Study of Brentuximab Vedotin in Patients With Relapsed or Refractory EBV-and CD30-positive Lymphomas”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2, 2019

Detailed Description

This is an open-label, non-randomized, multi-center, phase II trial of brentuximab vedotin to evaluate ORR primarily in patients with EBV- and CD30-positive lymphomas. The ORR will be evaluated based on the revised Cheson's criteria or modified SWAT criteria in case of cutaneous EBV- and CD30-positive lymphomas.

Interventions

  • Drug: brentuximab vedotin
    • Brentuximab vedotin administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle. The dose of brentuximab vedotin is 1.8 mg/kg q 3 weeks.

Arms, Groups and Cohorts

  • Experimental: Brentuximab vedotin
    • Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of the anti-CD30 chimeric immunoglobulin G1 (IgG1) monoclonal antibody cAC10 and the potent antimicrotubule drug monomethyl auristatin E connected by a protease-cleavable linker. cAC10 binds to the CD30 antigen, which has a very low expression on normal cells but is found on some tumor cells.

Clinical Trial Outcome Measures

Primary Measures

  • To evaluate the overall response rate (ORR) of brentuximab vedotin in EBV- and CD30-positive lymphomas
    • Time Frame: One-year
    • ORR using investigator assessments according SWAT

Secondary Measures

  • To evaluate the safety profile of brentuximab vedotin using CTCAE version 4.03
    • Time Frame: Until 1 month after the last dose of brentuximab vedotin
    • AEs/SAEs as defined by NCI CTCAE version 5.0
  • To calculate progression-free survival (PFS) time
    • Time Frame: One-year
    • PFS as defined as the time from the date of initiation until the date of first documented progression
  • To calculate the duration of response
    • Time Frame: One-year
    • 6weeks
  • To calculate overall survival (OS) time
    • Time Frame: One-year
    • OS as defined as the time from the date of first dose until death due to any cause

Participating in This Clinical Trial

Inclusion Criteria

1. Patients with relapsed or refractory EBV- and CD30-positive lymphomas

2. Age ≥ 18 years

3. ECOG performance status 0-2

4. At least one measurable lesion based on revised Cheson's or modified SWAT criteria

5. Provision archival tumor tissues (4 μm thickness x 5 unstained slides) and blood samples

6. Voluntary written informed consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

7. Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.

8. Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.

9. Adequate hematologic function: absolute neutrophil count (ANC) ≥1,500/µL, platelet count ≥ 75,000/µL, and hemoglobin ≥8.0 g/dL unless there is known hematologic tumor marrow involvement (ANC ≥ 1,000/µL and platelet count ≥ 50,000/µL if there is known bone marrow involvement)

10. Adequate liver function: total bilirubin < 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome and ALT or AST < 3 x ULN (AST and AST < 5 x ULN if their elevation can be reasonably ascribed to the presence of hematologic tumor in liver)

11. Adequate renal function: serum creatinine < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute.

12. Expected survival > 3 months

Exclusion Criteria

1. Female patient who are both lactating and breast-feeding or have a positive serum pregnancy test

2. Any serious medical or psychiatric illness

3. Known cerebral or meningeal involvement (EBV- and CD30-positive lymphoma or any other etiology), including signs or symptoms of PML

4. Symptomatic neurologic disease compromising normal activities or requiring medication

5. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2

6. Known history of myocardial infarction within 1 year, NYHA class III/IV heart failure, or uncontrolled cardiovascular conditions including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%.

7. Any active systemic viral, bacterial, or fungal infection within 2 weeks prior to first study drug dose

8. Any prior chemotherapy and/or other investigational agents within at least 5 half-lives of last dose

9. Prior stem cell transplantation within 100 days or radioimmunotherapy within 8 weeks

10. Prior exposure to CD30-targeted agents

11. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin

12. Known human immunodeficiency virus (HIV) positive

13. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection

14. Another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Seoul National University Hospital
  • Collaborator
    • Seoul National University Bundang Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Tae Min Kim, MD, PhD, Principal Investigator, Seoul National University Hospital

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