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

Diffuse Large B Cell Lymphoma Clinical Trial

— DLBCL  

Official title:

Phase II Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03681535
• Other study ID #: Pro00100510
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 13, 2019
• Est. completion date: August 2028

Study information

• Verified date: April 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 241
• Est. completion date: August 2028
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Radiation:
• Radiation Therapy
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.

Locations

Country	Name	City	State
Czechia	University Hospital Motol	Prague
Italy	University of Torino	Torino
Japan	Juntendo University	Tokyo
Korea, Republic of	Yonsei University Health System	Seoul
Singapore	National Cancer Center of Singapore	Singapore
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center	Milford	Massachusetts
United States	University of Rochester James P. Wilmot Cancer Institute	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital	Weymouth	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Countries where clinical trial is conducted

United States,  Czechia,  Italy,  Japan,  Korea, Republic of,  Singapore, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local control rate	Local control rate of 95% measured by standard of care imaging obtained per the National Comprehensive Cancer Network guidelines	5 years
Secondary	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.	5 years
Secondary	Overall Survival	Overall survival will be defines as the time from on-study to death due to any cause.	5 years
Secondary	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.	5 years