The standard chemotherapy for Hodgkin lymphoma is called ABVD which is a combination of 4 chemotherapy drugs (doxorubicin, bleomycin, vinblastine, and dacarbazine). The number of cycles of ABVD chemotherapy Hodgkin lymphoma patients receive is about 4-6 cycles. In addition to the ABVD chemotherapy, patients with Hodgkin lymphoma will routinely receive radiation therapy. The use of chemotherapy and radiation may cause long term treatment related side effects such as heart problems and other cancers. Researchers are trying to find if combining ABVD chemotherapy with new drugs and reducing the number of ABVD chemotherapy cycles given is just as effective as the standard Hodgkin treatment. Brentuximab vedotin is approved by the United States Food and Drug administration (FDA) for the treatment of Hodgkin lymphoma that has come back (relapsed). For this research study, the use of brentuximab vedotin in newly diagnosed Hodgkin lymphoma is considered investigational. Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of your immune system. They can stick to and attack specific targets on cells. The antibody part of the brentuximab vedotin sticks to a target called cluster of differentiation antigen 30 (CD30). CD30 is an important molecule on some cancer cells and some normal cells of the immune system. The purpose of this research study is to see the effects of treatment with fewer cycles of the combination chemotherapy, ABVD, followed by the study drug brentuximab vedotin has on study participants and Hodgkins lymphoma.
This study is designed as a single arm pilot feasibility trial using an induction of 2-6 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 6 cycles of brentuximab vedotin (SGN-35) consolidation for previously untreated patients with stage I and II non-bulky Hodgkin Lymphoma (HL). Feasibility will be determined by the percentage of patients who have no clinical evidence of HL, and achieve positron emission tomograph (PET) negative disease post brentuximab consolidation. We anticipate approximately 40 patients will be eligible across participating centers (including UNC, Mayo Clinic, and the UNC Cancer Network (UNCCN)) over a 2 year period. A future phase II study evaluating progression free survival (PFS) after ABVD followed by brentuximab vedotin will be considered feasible if ≥ 13 of 15 patients enrolled in this pilot trial become PET negative after brentuximab vedotin consolidation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
IV, 1.8mg/kg, every 3 weeks for 6 cycles.
Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles. Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Mayo Clinic
Rochester, Minnesota, United States
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Levine Cancer Istitute, Carolinas Health Care system
Charlotte, North Carolina, United States
Rex Cancer Center
Raleigh, North Carolina, United States
Vanderbilt University
Nashville, Tennessee, United States
Percentage of Patients With Positron Emission Tomography (PET) Negative Disease
Percentage of patients who convert to PET negative disease post consolidation. This is defined by PET with Deauville \<=2. The Deauville 5-point scoring system is a five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG Positron emission tomography: Score 1: No uptake above the background Score 2: Uptake ≤ mediastinum Score 3: Uptake \> mediastinum but ≤ liver Score 4: Uptake moderately increased compared to the liver at any site Score 5: Uptake markedly increased compared to the liver at any site Score X: New areas of uptake unlikely to be related to lymphoma
Time frame: 12 months
Number of Participant Who Achieved a Complete Response
Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Time frame: 12 months
Conversion Rate to Complete Response. Number of Participants Who Had a Partial Response Post ABVD Who Converted to a Complete Response.
Conversion rate to Complete Response after brentuximab vedotin in patients with partial response at the end of ABVD therapy. Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to all of the following: they should be clearly measurable in at least 2 perpendicular dimensions; if possible they should be from disparate regions of the body; and they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
Time frame: 12 months
3 Year Progression Free Survival Rate
Defined as the percentage of participants who did not show relapse/progression or death from any cause occurred at 3 years after the time from ABVD treatment start. Relapse/progression is measured using the Revised Response Criteria for Malignant Lymphoma and is defined as the following: appearance of any new lesion \> 1.5 centimeters (cm) in any axis during or at the end of therapy; at least a 50% increase from nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions; or at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis. In addition, lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was positron emission tomography (PET) positive before therapy
Time frame: 3 years
3 Year Time to Progression Rate
Defined as the percentage of participants who did not show relapse/progression at 3 years after the time from ABVD treatment start. Relapse/progression is measured using the Revised Response Criteria for Malignant Lymphoma and is defined as the following: appearance of any new lesion \> 1.5 centimeters (cm) in any axis during or at the end of therapy; at least a 50% increase from nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions; or at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis. In addition, lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was positron emission tomography (PET) positive before therapy
Time frame: 3 years
Number of Adverse Events Attributed to Brentuximab Vedotin With a Grade 3 or Higher
Number of adverse events attributed to Brentuximab Vedotin with a grade 3 or higher. Toxicity assessed via the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.The higher the grade the more severe the adverse event.
Time frame: 12 months
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