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

• Sponsor: Duke University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03681535
• Collaborator: (none)
• Enrollment: 240
• Locations: 14
• Arm: 1
• Anticipated Duration (Months): 164.6
• Patients Per Site: 17.1
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma	Radiation: Radiation Therapy	N/A

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 240 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma
• Actual Study Start Date: Feb 13, 2019
• Anticipated Primary Completion Date: Nov 1, 2027
• Anticipated Study Completion Date: Nov 1, 2032

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Single arm interventional study 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).

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.

Outcome Measures

Primary Outcome Measures

1. Local control rate [5 years]

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

Secondary Outcome Measures

1. Disease-free survival [5 years]

   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.

2. Overall Survival [5 years]

   Overall survival will be defines as the time from on-study to death due to any cause.

3. Patterns of failure [5 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center	Milford	Massachusetts	United States	01757
4	Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital	Weymouth	Massachusetts	United States	02190
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
7	University of Rochester James P. Wilmot Cancer Institute	Rochester	New York	United States	14642
8	Duke University Medical Center	Durham	North Carolina	United States	27710
9	MD Anderson Cancer Center	Houston	Texas	United States	77030
10	University Hospital Motol	Prague		Czechia
11	University of Torino	Torino		Italy
12	Juntendo University	Tokyo		Japan
13	Yonsei University Health System	Seoul		Korea, Republic of
14	National Cancer Center of Singapore	Singapore		Singapore

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Christopher Kelsey, MD, Duke Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03681535
• Other Study ID Numbers: Pro00100510
• First Posted: Sep 24, 2018
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Duke University: DLBCL; Reduce radiation dose
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

No Results Posted as of Jul 20, 2022