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

• ClinicalTrials.gov Identifier: NCT03681535
• Recruitment Status: Active, not recruiting
• First Posted: September 24, 2018
• Last Update Posted: April 22, 2024
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Tracking Information

• First Submitted Date: September 20, 2018
• First Posted Date: September 24, 2018
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: February 13, 2019
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 20, 2018)

Local control rate [ Time Frame: 5 years ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 20, 2018)

• Disease-free survival [ Time Frame: 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.
• Overall Survival [ Time Frame: 5 years ]
  Overall survival will be defines as the time from on-study to death due to any cause.
• Patterns of failure [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diffuse Large B Cell Lymphoma

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.

Study Arms

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).

Intervention: Radiation: Radiation Therapy

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 16, 2023): 241
• Original Estimated Enrollment (submitted: September 20, 2018): 40
• Estimated Study Completion Date: August 2028
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, Italy, Japan, Korea, Republic of, Singapore, United States

Administrative Information

• NCT Number: NCT03681535
• Other Study ID Numbers: Pro00100510
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Duke University
• Original Responsible Party: Same as current
• Current Study Sponsor: Duke University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christopher Kelsey, MD; Duke Health

• PRS Account: Duke University
• Verification Date: April 2024