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

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Radiation Therapy
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring DLBCL, Reduce radiation dose

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana Farber Cancer Institute
  • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
  • Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital
  • Mayo Clinic
  • Washington University School of Medicine
  • University of Rochester James P. Wilmot Cancer Institute
  • Duke University Medical Center
  • MD Anderson Cancer Center
  • University Hospital Motol
  • University of Torino
  • Juntendo University
  • Yonsei University Health System
  • National Cancer Center of Singapore

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm interventional study

Arm Description

RT 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).

Outcomes

Primary Outcome Measures

Local control rate
Local control rate of 95% measured by standard of care imaging obtained per the National Comprehensive Cancer Network guidelines

Secondary Outcome Measures

Disease-free survival
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.
Overall Survival
Overall survival will be defines as the time from on-study to death due to any cause.
Patterns of failure
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.

Full Information

First Posted
September 20, 2018
Last Updated
August 16, 2023
Sponsor
Duke University
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1. Study Identification

Unique Protocol Identification Number
NCT03681535
Brief Title
Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma
Acronym
DLBCL
Official Title
Phase II Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 13, 2019 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma
Keywords
DLBCL, Reduce radiation dose

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
241 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single arm interventional study
Arm Type
Experimental
Arm Description
RT 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).
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention Description
This phase II study will evaluate whether a reduction in the RT dose, concomitant with a decrease in the RT field size, in patients that achieve complete response and have a negative post-chemotherapy PET scan following 3 to 6 cycles of rituximab containing chemotherapy, will be associated with a low risk of in-field failure. The goal of this approach is to maintain excellent control rates while minimizing the risk of acute and late toxicity.
Primary Outcome Measure Information:
Title
Local control rate
Description
Local control rate of 95% measured by standard of care imaging obtained per the National Comprehensive Cancer Network guidelines
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Disease-free survival
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.
Time Frame
5 years
Title
Overall Survival
Description
Overall survival will be defines as the time from on-study to death due to any cause.
Time Frame
5 years
Title
Patterns of failure
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.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Kelsey, MD
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
City
Milford
State/Province
Massachusetts
ZIP/Postal Code
01757
Country
United States
Facility Name
Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital
City
Weymouth
State/Province
Massachusetts
ZIP/Postal Code
02190
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Rochester James P. Wilmot Cancer Institute
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University Hospital Motol
City
Prague
Country
Czechia
Facility Name
University of Torino
City
Torino
Country
Italy
Facility Name
Juntendo University
City
Tokyo
Country
Japan
Facility Name
Yonsei University Health System
City
Seoul
Country
Korea, Republic of
Facility Name
National Cancer Center of Singapore
City
Singapore
Country
Singapore

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30858144
Citation
Kelsey CR, Broadwater G, James O, Chino J, Diehl L, Beaven AW, Chang C, Koontz BF, Prosnitz LR. Phase 2 Study of Dose-Reduced Consolidation Radiation Therapy in Diffuse Large B-Cell Lymphoma. Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):96-101. doi: 10.1016/j.ijrobp.2019.02.055. Epub 2019 Mar 8.
Results Reference
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Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma

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