Clinical trial NCT03681535: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Diffuse Large B Cell Lymphoma
Keywords: DLBCL
Reduce radiation dose
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2018-09-24
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Local control rate
timeFrame: 5 years
Secondary outcomes:
measure: Disease-free survival
timeFrame: 5 years
measure: Overall Survival
timeFrame: 5 years
measure: Patterns of failure
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Weymouth
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: University of Rochester James P. Wilmot Cancer Institute
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Prague
country: Czechia
facility: University Hospital Motol
city: Torino
country: Italy
facility: University of Torino
city: Tokyo
country: Japan
facility: Juntendo University
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System
city: Singapore
country: Singapore
facility: National Cancer Center of Singapore
Study officials:
affiliation: Duke Health
name: Christopher Kelsey, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.