Brentuximab Vedotin, Bendamustine, and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Launched by UNIVERSITY OF ARIZONA · Dec 3, 2015

Keywords

ClinConnect Summary

PRIMARY OBJECTIVES:

I. Complete response (CR) rate and overall response rate (ORR) for patients with relapsed aggressive high-risk non-Hodgkin lymphoma (NHL) treated with brentuximab vedotin, bendamustine and rituximab (S-BR).

SECONDARY OBJECTIVES:

I. To estimate 2-year progression-free survival (PFS). II. To evaluate rate of positron emission tomography (PET)-CR and correlation to 2 year PFS.

III. To evaluate the toxicity of six cycles of S-BR. IV. To evaluate mobilization, stem cell collection, engraftment in patients that proceed to salvage autologous stem cell transplant (ASCT).

SC...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• * CD30 detectable B lineage relapsed refractory NHL including the following histologies:
• • Aggressive lymphomas: diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, grey zone lymphomas, high grade B cell lymphomas, and transformed indolent lymphomas
• * Indolent lymphoma: follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma; indolent lymphoma patients eligible for this trial should have high tumor burden and high risk disease, as defined by:
• • The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
• • Intermediate or high risk by Follicular Lymphoma International Prognostic Index (FLIPI) score or elevated lactose dehydrogenase (LDH)/ beta-2 microglobulin (B2M)
• • Subjects between 18 and 75 years old. Subjects older than 75 years old to be discussed with PI prior to subject consent; consensus between PI and treating physician is required.
• • Karnofsky performance status (KPS) \>= 70%, Eastern Cooperative Oncology Group (ECOG) =\< 2
• • At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
• • Patients must have received at least one but no more than 4 prior lines of systemic therapy
• • American Heart Association (AHA) class 1 without significant limitation of physical activity
• • Ejection fraction (EF) of at least \>= 40% by multigated acquisition (MUGA) or echocardiography (ECHO)
• • Total bilirubin =\< 1.5 mg/dl
• • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 2.5 times the upper limit of normal without evidence of active infectious hepatitis
• • Creatinine clearance \>= 40 ml/min
• • Platelets \> 75,000 cells/ul
• • Absolute neutrophil count (ANC) \> 1,000 cells/ul
• • Ability to provide informed consent
• • Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) pregnancy test at screening; pregnancy testing is not required for: (a) women who have been post-menopausal for at least 2 years without menses; or (b) women who are surgically sterile (e.g. by means of hysterectomy, tubal ligation, etc.)
• • Males and females of childbearing potential must be able and willing to use an effective contraceptive method during treatment and for three months after completing treatment
• Exclusion Criteria:
• • Active infections (bacterial, fungal, or viral)
• • Evidence of sanctuary site involvement by disease, e.g., central nervous system, ocular, testicular involvement
• • Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
• • Recent chemotherapy within 3 weeks of screening
• • Major surgery within 4 weeks of screening
• • Diagnosed or treated for malignancy other than NHL for which patient will be treated, except: malignancy treated with curative intent and with no known active disease present for \>= 3 years before subject registration; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease
• • History of stroke or intracranial hemorrhage within 6 months prior to registration
• • Requires anticoagulation with warfarin or equivalent vitamin K antagonists
• • Requires treatment with strong cytochrome (CYP3A4/5) inhibitors
• • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• • Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
• • Women who are pregnant or breastfeeding
• • Prior use of brentuximab vedotin
• • Prior use of bendamustine for indolent lymphoma allowed if \> 2 years, CR to bendamustine and well tolerated with no residual \> grade 1 toxicity; no prior use of bendamustine for aggressive lymphoma allowed
• • Prior allogeneic transplant
• • Patients with Child-Pugh B or C hepatic impairment