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Pilot Study of Brentuximab Vedotin in CD30 Positive EBV Positive Diffuse Large B-Cell Lymphomas of the Elderly

18 Years
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Trial Information

Pilot Study of Brentuximab Vedotin in CD30 Positive EBV Positive Diffuse Large B-Cell Lymphomas of the Elderly

Brentuximab vedotin is a type of drug called an antibody drug conjugate (ADC). ADCs usually
have 2 parts; a part that targets cancer cells (the antibody) and a cell killing part (the
chemotherapy). Antibodies are proteins that are part of the immune system. They can stick to
and attack specific targets on cells. The antibody part of brentuximab vedotin sticks to a
target called CD30. CD30 is an important molecule on some cancer cells (including
non-Hodgkin lymphoma) and some normal cells of the immune system. The cell killing part of
brentuximab vedotin is a chemotherapy called monomethyl auristatin E (MMAE). After the
brentuximab vedotin attaches to the CD30 part of the cell, the MMAE enters the cell and
kills it.

More than 350 people with cancer have already been given brentuximab vedotin in research
studies. These research studies were done to test the safety of different doses of
brentuximab vedotin and to find out if brentuximab vedotin is active against cancer.

Inclusion Criteria:

- Confirmed diagnosis of CD30+EBV+DLBCLE (EDLBCLE). Diagnosis will be based on
identification of diffuse large cell lymphoma (DLBCL) in biopsy specimens
characterized by positivity in the malignant cell population of 2 principal markers:

- CD30 by immunohistochemistry (IHC) and

- Epstein-Barr virus (EBV) by EBER in situ hybridization (ISH)

- Histology slides and pathology material must be available at the site for each
patient before enrollment in order to be sent to the Leading Institution of the study
for central pathology review and pharmacodynamic studies.

- Patients must have progressive, relapsed or refractory disease after:

- At least one prior systemic anti-lymphoma regimen (chemotherapy or

- Relapsed or failed autologous or allogeneic stem cell transplant.

- Understand and voluntarily sign an Institutional Review Board (IRB) approved informed
consent form

- Must have at least one site of disease (index lesion) measurable in two dimensions by
computed tomography (CT)

- At least 4 weeks since the last chemotherapy, radiation therapy, immunotherapy or any
investigational non-immunotherapy products with clinical evidence of recovery from
any toxicity associated with such treatment

- Must meet the following criteria within 4 days before the first dose of study drug:

- Neutrophils ≥1,000/ul

- Hemoglobin ≥ 8 g/dL

- Platelets≥ 50.0x10^9 /L

- Total bilirubin ≤ 1.5 x upper normal limit, or ≤ 5 x upper normal limit if
documented hepatic involvement with lymphoma or history of Gilbert's Syndrome

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper
normal limit (≤ 5 x upper normal limit if documented hepatic involvement with

- Calculated creatinine clearance ≥ 40 mL/min/1.73 m^2 based on Cockcroft and
Gault method

- Prothrombin time (PT) or international normalization ratio (INR), and activated
partial thromboplastin time (APTT) ≤ 1.5 x upper limit of normal (ULN) unless
patient is receiving anticoagulants. If patient is on anticoagulation therapy,
levels should be within therapeutic range.

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Negative pregnancy test for women of childbearing potential

- Recovered (≤ Grade 1 toxicity) from the reversible effects of prior antineoplastic

Exclusion Criteria:

- Any of the following cardiovascular conditions or values within 6 months before the
first dose of study drug: Myocardial infarction and the New York Heart Association
(NYHA) Class III or IV heart failure.

- History of another primary malignancy not in remission for at least 3 years; except
adequately treated patients with completely resected in situ carcinoma, such as
nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous
intraepithelial lesion on Pap smear

- Known active cerebral/meningeal involvement with lymphoma. Asymptomatic patients with
previously treated and resolved central nervous system (CNS) lymphoma involvement are

- Prior administration of Brentuximab vedotin

- Corticosteroid monotherapy for lymphoma within 2 weeks of the first dose of study

- Radioimmunotherapy administration within 8 weeks before the first dose of study drug

- Any serious underlying medical condition that, in the opinion of the investigator or
medical monitor, would impair the ability to receive or tolerate the planned

- Known hypersensitivity to recombinant proteins, or any component contained in the
drug formulation

- Female patients who are lactating or have a positive serum pregnancy test during the
screening period or a positive urine pregnancy test on Day 1 before first dose of
study drug

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective Response Rate (ORR)

Outcome Description:

The primary efficacy parameter is objective response rate, defined as the proportion of patients with complete response (CR) and partial response (PR). To evaluate the activity of Brentuximab vedotin in patients with refractory/relapsed EDLBCLE using modified International Working Group (IWG) response criteria for malignant lymphoma. Measurable lesions: Lesions that can be measured accurately in at least one dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques, or as ≥10 mm with spiral CT scan. Nonmeasurable lesions: Lesions not classified as measurable lesions (longest diameter ≤20 mm with conventional techniques or ≤10 mm with spiral CT scan. Frequencies and percentages will be used to summarize for all response categories. The ORR, our primary endpoint, and its 95 confidence interval will be calculated using the exact binominal method.

Outcome Time Frame:

36 months

Safety Issue:


Principal Investigator

Lubomir Sokol, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

October 2016

Related Keywords:

  • Lymphoma
  • positive
  • diffuse
  • B-Cell
  • elderly
  • EBV
  • malignant
  • pilot
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612