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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: Phase II Study of Brentuximab Vedotin in Combination With Bendamustine and Rituximab, in Patients With CD30 Positive, Relapsed or Refractory B Cell Non-Hodgkin Lymphoma (NHL)

Brief Summary: 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.

Detailed 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).

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.

  • CR rate [ Time Frame: Up to 2 years after completion of study treatment ]
    The complete response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
  • Percentage of patients obtaining a CR + PR using Cheson criteria [ Time Frame: Up to 2 years after completion of study treatment ]
    The overall response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.


    • Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Median time to progression [ Time Frame: At 2 years ]
    • PFS [ Time Frame: At 2 years ]
      PFS will be estimated using the Kaplan-Meier estimate, with stratification by allogeneic stem cell transplantation status.
    • Complete response rate assessed by PET/CT [ Time Frame: Up to 2 years after the completion of study treatment ]
      The complete response rate by PET/CT will be estimated with the 95% exact confidence interval.
    • Frequency of adverse events (AEs) and serious AEs assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years after completion of study treatment ]
      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.
    • CD34+ peripheral blood stem cells assessed by flow cytometry [ Time Frame: Up to 2 years after completion of study treatment ]
      Only for subjects receiving transplant
    • Median time to engraftment [ Time Frame: Up to 2 years after completion of study treatment ]
      Only for subjects receiving transplant
    • Soluble CD30 levels in blood by biochemical assay [ Time Frame: 48-72 hours after brentuximab vedotin treatment ]
      Brentuximab vedotin pharmacokinetics in combination therapy will be measured and correlated to single agent data.


    Original Secondary Outcome: Same as current

    Information By: University of Arizona

    Dates:
    Date Received: September 24, 2015
    Date Started: December 16, 2015
    Date Completion:
    Last Updated: May 18, 2017
    Last Verified: May 2017