This phase II trial studies how well brentuximab vedotin, bendamustine, and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, use antibody to target chemotherapy in cancer cells. Drugs used in chemotherapy, such as bendamustine, work in different ways to kill cancer cells. Monoclonal antibodies, such as rituximab, kill the cancer cells directly, but also harness the immune system to kill the cancer cells. Adding brentuximab to rituximab may improve response rates in CD30 positive, CD20 positive Relapsed Refactory NHL.
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). SCIENTIFIC OBJECTIVES: I. To evaluate percentage of tumor cells that are positive or negative for cluster of differentiation (CD)30 by immunohistochemistry (IHC), the subcellular location of CD30 (membrane or cytoplasmic only with absence of membrane expression), intensity of scoring, and correlating with clinical outcomes. II. To evaluate gene expression profiling (GEP) by Nanostring Technology and comparing expression levels of target genes in CD30 membrane positive, CD30 cytoplasmic only positive or CD30 negative tumor cells. III. To evaluate correlation between mutations identified through next generation sequencing (NGS) including ribonucleic acid (RNA) sequencing of the tumor transcriptome, and correlating to GEP and CD30 IHC, and correlating to clinical outcomes. IV. To evaluate the levels of soluble CD30 at baseline and in response to treatment. SCHEDULE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1, bendamustine IV over 30-60 minutes on days 1-2, and rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Brentuximab vedotin IV over 30 minutes on day 1.Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Bendamustine IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Arizona Cancer Center at UMC North
Tucson, Arizona, United States
CR rate
The complete response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Time frame: Up to 2 years after completion of study treatment
Percentage of patients obtaining a CR + PR using Cheson criteria
The overall response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Time frame: Up to 2 years after completion of study treatment
Median time to progression
Time frame: At 2 years
PFS
PFS will be estimated using the Kaplan-Meier estimate, with stratification by allogeneic stem cell transplantation status.
Time frame: At 2 years
Complete response rate assessed by PET/CT
The complete response rate by PET/CT will be estimated with the 95% exact confidence interval.
Time frame: Up to 2 years after the completion of study treatment
Frequency of adverse events (AEs) and serious AEs assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
The proportion of patients with treatment-emergent AEs will be tabulated, including by causality, seriousness, severity/grade, and whether the AE resulted in death or discontinuation of treatment.
Time frame: Up to 2 years after completion of study treatment
CD34+ peripheral blood stem cells assessed by flow cytometry
Only for subjects receiving transplant
Time frame: Up to 2 years after completion of study treatment
Median time to engraftment
Only for subjects receiving transplant
Time frame: Up to 2 years after completion of study treatment
Soluble CD30 levels in blood by biochemical assay
Brentuximab vedotin pharmacokinetics in combination therapy will be measured and correlated to single agent data.
Time frame: 48-72 hours after brentuximab vedotin treatment
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