This phase II trial evaluates how a biomarker called circulating tumor deoxyribonucleic acid (ctDNA) correlates with positron emission tomography (PET) results and uses PET-determined disease response to guide therapy in patients receiving a standard treatment regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without radiation) for limited stage diffuse large B cell lymphoma. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body’s immune response. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell’s DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. PET scans are commonly used radiologic tests to determine how much lymphoma is present in the body before and after treatment. A new way to evaluate disease in the body uses ctDNA (through a blood test). Tumor DNA is the genetic information inside cells. The results of this study may establish whether a relationship exists between ctDNA and PET scan results. If a relationship is established, ctDNA (rather than PET scans) may be used in the future to adapt a patient's treatment and/or identify response to treatment, inducing whether or not a patient's disease is coming back.
Additional locations may be listed on ClinicalTrials.gov for NCT03758989.
Locations matching your search criteria
United States
New York
Rochester
University of RochesterStatus: Active
Contact: Carla Casulo
Phone: 585-275-5863
PRIMARY OBJECTIVE:
I. To determine the correlation between fluorodeoxyglucose positron emission tomography (FDG-PET) and minimal residual disease (MRD), as measured by circulating tumor plasma DNA (ctDNA) in patients with early stage diffuse large B cell lymphoma (DLBCL).
SECONDARY OBJECTIVES:
I. To determine PET complete response (CR) rate.
II. To determine the association between change in MRD from baseline to time of re-staging PET and progression free survival (PFS).
III. To determine the association between change in MRD from baseline to time of re-staging PET and re-staging Deauville score.
IV. To assess the diagnostic ability of baseline MRD to determine if radiation therapy is necessary after 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP).
V. To describe toxicity rates using Common Terminology Criteria for Adverse Events (CTCAE) 4.03.
VI. To measure changes in quality of life using Patient Reported Outcomes Measurement Information System (PROMIS) scale.
VII. To assess PFS and overall survival (OS) of patients through two years of follow-up.
OUTLINE:
Patients receive rituximab intravenously (IV) on day 1 of cycle 1, rituximab and hyaluronidase human subcutaneously (SC) on day 1 of cycles 2 and 3, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 of each cycle, and prednisone orally (PO) once daily (QD) on days 1-5 of each cycle. Cycles repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. After 3 cycles, patients undergo FDG-PET for response assessment. Patients with complete response (Deauville score of 1, 2, or 3 [negative FDG-PET scan]) after 3 cycles proceed to cycle 4 and receive rituximab and hyaluronidase human SC, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 of cycle 4, and prednisone PO QD on days 1-5 of cycle 4. Patients with active disease (Deauville score of 4) after 3 cycles proceed to cycle 4 and receive rituximab and hyaluronidase human SC, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 of cycle 4, prednisone PO QD on days 1-5 of cycle 4, and also undergo involved-site radiation therapy (ISRT) with integrated boost starting between days 15-18 of cycle 4. Patients with residual disease and Deauville score of 5 after 3 cycles are taken off study.
Patients undergo FDG-PET and collection of blood samples throughout the study. Patients may undergo CT scan during follow up if clinically indicated.
After completion of study treatment, patients are followed up at 3 months and then every 3 months for year 1 (months 6, 9, 12), every 6 months for year 2 (months 18, 24) and then yearly in years 3-5 (months 26, 48, 60).
Lead OrganizationUniversity of Rochester
Principal InvestigatorCarla Casulo
