Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Brentuximab Vedotin and Lenalidomide in Treating Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Protocol: OSU-14267

Full Title

A Phase I Trial of Brentuximab Vedotin in Combination with Lenalidomide in Relapsed or Refractory Diffuse Large B-cell Lymphoma


This phase I trial studies the side effects and best dose of brentuximab vedotin when given together with lenalidomide in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement or has not responded to treatment. Monoclonal antibodies, such as brentuximab vedotin, find cancer cells and help carry cancer-killing substances to them. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving brentuximab vedotin with lenalidomide may kill more cancer cells.

Study Objective


I. To determine the safety and maximum tolerated dose (MTD) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL).


I. To test the potential association between cluster of differentiation (CD)30 expression on tumor cells and clinical efficacy of the combination of brentuximab vedotin and lenalidomide.

II. To evaluate the efficacy of brentuximab vedotin (BV) and lenalidomide in the subsets of activated B cell-like and germinal center B cell-like DLBCL based on the Hans criteria.

III. To determine efficacy of brentuximab vedotin and lenalidomide in relapsed/refractory DLBCL as measured by the overall response rate (complete response [CR] + partial response [PR]), duration of response, and progression free survival (PFS).


I. To determine T-cell and natural killer (NK) cell subset numbers, phenotype, and functional status in rel/ref DLBCL patients, and whether the combination of brentuximab vedotin and lenalidomide alters these parameters during therapy.

II. To determine changes in plasma cytokine levels and other biomarkers in this patient population during therapy with the combination of brentuximab vedotin and lenalidomide.

III. To investigate for the presence of recurrent genomic mutations in pretreatment biopsies and correlate with therapy response.

OUTLINE: This is a dose-escalation study.

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and lenalidomide orally (PO) once daily (QD) on days 1-21 (except dose level 2 days 1-14). Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

Patients with a CR, PR, or stable disease (SD) at the completion of 16 courses may continue to receive treatment with brentuximab vedotin and lenalidomide at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 28-35 days, every 3 months for 2 years, and then per institutional standard of care thereafter.

Are you eligible?

Inclusion Criteria:

Relapsed or refractory de novo or transformed DLBCL disease following at least one prior systemic therapy (for DLBCL)

CD30 immunohistochemical staining using the anti-CD30 Becton Dickinson monoclonal (BerH2) antibody must be available on the most recent biopsy specimen; during dose escalation, patients can be either CD30 positive or CD30 negative; during dose expansion, 15 patients must be CD30 positive and 15 patients must be CD30 negative

Post-autologous stem cell transplant (ASCT) or not a candidate for ASCT; prior allogeneic stem cell transplant is allowed if patient is off all immunosuppressives and has no evidence of active graft-versus-host disease (GVHD)

Prior treatment with brentuximab vedotin is allowed provided the patient did not progress on BV or within 30 days of last dose of BV; patients must be at least 3 months from the last dose of BV

Bidimensional measurable disease of at least 1.5 cm in the greatest transverse diameter as documented by computed tomography (CT) or positron emission tomography (PET)/CT

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Absolute neutrophil count (ANC) >= 1,000/mcl

Platelets >= 50,000/mcl

Serum bilirubin =< 1.5 x institutional upper limit of normal (IULN) OR serum bilirubin =< 3.0 x IULN for patients with Gilbert’s disease or documented hepatic involvement with non-Hodgkin lymphoma (NHL)

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x IULN OR ALT and AST =< 5.0 x IULN for patients with documented hepatic involvement with NHL

Creatinine clearance >= 60 mL/min/1.73 m^2 as calculated by Cockcroft-Gault

Women of childbearing potential must follow pregnancy testing requirements; this is defined as either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last doses of brentuximab vedotin and lenalidomide; women of childbearing potential must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately

All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program and be willing to comply with its requirements; per standard Revlimid REMS® program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS® program

Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria:

Primary mediastinal B-cell lymphoma

A history of other primary invasive malignancy that has not been in remission for at least 3 years or a current diagnosis of myelodysplastic syndrome (MDS) or an immature leukemia such as acute myeloid leukemia (AML)

Known active cerebral/meningeal lymphoma

Present or history of progressive multifocal leukoencephalopathy (PML)

New York Heart Association (NYHA) class III or IV congestive heart failure

Active Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 3 or higher viral, bacterial, or fungal infection

Known to be positive for hepatitis B by surface antigen expression and hepatitis B core antibody

Known to have active hepatitis C infection (positive by polymerase chain reaction) or on antiviral therapy for hepatitis C within 6 months prior to the first doses of brentuximab vedotin and lenalidomide

Known to be positive for human immunodeficiency virus (HIV)

Receiving chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed at least 3 weeks prior to study entry, unless underlying disease is progressing on therapy

Currently receiving any other investigational agents

Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin or lenalidomide

Pregnant and/or breastfeeding; women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide

Receiving immunosuppressive therapy

Refractory to prior therapy with brentuximab vedotin (evidence of progression within 30 days of the last dose)

Prior therapy with lenalidomide

Non-Hodgkin’s Lymphoma (B- & T-Cell) Lymphoma