Clinical Trials /

Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma

NCT03681535

Description:

This phase II study will evaluate whether a reduction in radiation dose and field size will maintain a high rate of local control while minimizing the risk of acute and late toxicity . Hypothesis: The radiation dose and treatment volume can be safely reduced from 30 Gy to 20 Gy while maintaining high rates of local control in patients who had a negative PET-CT scan following rituximab - containing chemotherapy.

Related Conditions:
  • B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma Activated B-Cell Type
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma
  • High Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Recruiting

Phase:

N/A

URL:

https://clinicaltrials.gov/show/NCT03681535

Trial Eligibility

Document

Title

  • Brief Title: Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma
  • Official Title: Phase II Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: Pro00100510
  • NCT ID: NCT03681535

Conditions

  • Diffuse Large B Cell Lymphoma

Purpose

This phase II study will evaluate whether a reduction in radiation dose and field size will maintain a high rate of local control while minimizing the risk of acute and late toxicity . Hypothesis: The radiation dose and treatment volume can be safely reduced from 30 Gy to 20 Gy while maintaining high rates of local control in patients who had a negative PET-CT scan following rituximab - containing chemotherapy.

Detailed Description

      Chemotherapy followed by consolidation radiation therapy (RT) is a recognized treatment
      paradigm for DLBCL. This was initially established based on the results of 2 randomized
      trials conducted in the 1980s-1990s. In these studies patients were treated with 30Gy after
      chemotherapy (ECOG study) or 40-55Gy (SWOG study). A British National Lymphoma Investigation
      study showed no difference in freedom from local progression, progression-free survival or
      overall survival in between patients receiving 30Gy and 40-45Gy. Additionally systemic
      therapy for DLBCL has significantly improved since these initial studies, with the addition
      of rituximab to standard chemotherapy.

      In a phase II study at Duke University patients with DLBCL NOS or primary mediastinal B-cell
      lymphoma were treated to 19.5-20Gy after achieving complete response to 4-6 cycles of
      chemotherapy containing rituximab. With a median follow-up of 43 months, there was only 1
      local recurrence. The 5-year local control rate was 98%. Progression-free and overall
      survival at 5 years was 81% and 88%. Therefore, there is emerging evidence of long term
      favorable outcomes in localized DLBCL, while decreasing the risk of late effects by reducing
      the dose and volume of RT.

      All participants will receive 20Gy instead of 30-36Gy after completion of at least 3 cycles
      of rituximab with combination chemotherapy. Participants must have a negative post
      chemotherapy PET-CT to participate in this study.

Trial Arms

NameTypeDescriptionInterventions
Single arm interventional studyExperimentalRT to 19.5-20Gy is given after 3 cycles of rituximab containing chemotherapy. RT is administered daily, 5 days per week in 1.5-2Gy fractions (treatments).

    Eligibility Criteria

            Inclusion Criteria:

          -  Histologic documentation of stage I-IV diffuse large B-cell lymphoma, not otherwise
             specified (DLBCL NOS), as defined by the 2016 WHO classification. This would include
             all entities within this category including germinal center B-cell and non-germinal
             center B-cell subtypes and those with a double expressor phenotype. Also eligible are
             stage I-IV high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements and
             high-grade B-cell lymphoma, NOS

          -  Completion of at least 3 cycles of rituximab-containing, anthracycline-based
             combination chemotherapy

          -  Negative post-chemotherapy PET-CT scan or negative interim PET-CT scan performed
             within 2 weeks of the final cycle of chemoimmunotherapy. This is defined as a score of
             1-3 on the PET Five Point (Deauville) Scale using the Modified Lugano Response
             Criteria for Non-Hodgkin's Lymphoma

          -  Absolute neutrophil count greater than 1000 and platelet count greater than 40,000

          -  Negative pregnancy test in women of child-bearing potential

          -  Signed study specific informed consent

        Exclusion Criteria:

          -  Primary central nervous system lymphoma, primary cutaneous DLBCL, leg type.
             T-cell/histiocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large
             B-cell lymphoma, or other distinct non-Hodgkin lymphomas arising from large B-cells
             included in the WHO classification

          -  Any absolute contraindications to irradiation
    Maximum Eligible Age:80 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Local control rate
    Time Frame:5 years
    Safety Issue:
    Description:Local control rate of 95% measured by standard of care imaging obtained per the National Comprehensive Cancer Network guidelines

    Secondary Outcome Measures

    Measure:Disease-free survival
    Time Frame:5 years
    Safety Issue:
    Description:Disease-free survival (DFS) will be defined as the time from on-study to first disease progression or death due to any cause, whichever comes first.
    Measure:Overall Survival
    Time Frame:5 years
    Safety Issue:
    Description:Overall survival will be defines as the time from on-study to death due to any cause.
    Measure:Patterns of failure
    Time Frame:5 years
    Safety Issue:
    Description:To examine patterns of failure we, we will tabulate the various ways that patients failed, up until the time of analysis. For example, these ways will include local only, local + distant, and distant only.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Duke University

    Trial Keywords

    • DLBCL
    • Reduce radiation dose

    Last Updated

    July 26, 2021