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

Phase 2

Completed

• Conditions: Relapsed or Refractory EBV-and CD30-positive Lymphomas
• Interventions: Drug: brentuximab vedotin

• Registration Number: NCT02388490
• Lead Sponsor: Seoul National University Hospital

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2015-02-04
• Study First Submitted QC: 2015-03-09
• Study First Posted: 2015-03-17
• Study Start: 2016-03-25
• Status Verified: 2019-04
• Primary Completion: 2019-04-02
• Study Completion: 2019-04-02
• Last Update Submitted: 2019-10-31
• Last Update Posted: 2019-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Brentuximab vedotin	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.

Primary Outcome Measures

Name	Time	Method
To Evaluate the Overall Response Rate (ORR) of Brentuximab Vedotin in EBV- and CD30-positive Lymphomas	One-year	The primary endpoint was the ORR based on the revised criteria or modified Severity Weighted Assessment Tool (SWAT) criteria in the case of cutaneous lymphomas.

Secondary Outcome Measures

Name	Time	Method
To Evaluate the Safety Profile	From the first dose of brentuximab vedotin to up to 30 days after the last dose, a total of up to approximately 366 days	AEs/SAEs occurring during the study period defined by CTCAE version 4.03
To Calculate Progression-free Survival (PFS) Time	One-year	PFS as defined as the time from the date of initiation until the date of first documented progression.; Revised tumor response criteria for lymphoma(Revised Cheson) or revised SWAT and assessed by MRI except a pregnant patient whose response evaluation can be assessed by CT scan: Progression is defined using these criteria, as observation of a new lesion or an increase of 50% or more from the nadir in a previously involved site.
To Calculate the Duration of Response	From the first dose Up to the time of data cut-off.	The duration of response was assessed in 12 patients who had objective responses. The response continued even after the completion of the planned 16 cycles of brentuximab vedotin administration in three of these 12 patients (25%) at the time of data cut-off.
To Calculate Overall Survival (OS) Time	From first dose to end of data collection	OS as defined as the time from the date of first dose until death due to any cause.; The median overall survival was obtained, but the upper value of 95% Confidence Interval was not reached at the time of data cut-off. Therefore the longest OS was 30.4 months, the follow-up duration up to the date of data cut-off.

Trial Locations

Locations (3)

Seoul National Unversity Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam, Korea, Republic of

SMG-SNU Boramae Medical Center; 🇰🇷 Seoul, Korea, Republic of