This phase II trial studies how well giving brentuximab vedotin together with combination chemotherapy works in treating older patients with previously untreated stage II-IV Hodgkin lymphoma (HL). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine (AVD), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin, doxorubicin hydrochloride, vinblastine, and dacarbazine together may kill more cancer cells.
LEAD IN: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. AVD CHEMOTHERAPY: Patients then receive doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving CR receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Given IV
Given IV
Given IV
Given IV
Ancillary studies
Optional correlative studies
Optional correlative studies
Correlative studies
Correlative studies
Optional correlative studies
Optional correlative studies
Optional correlative studies
Stanford University Medical Center
Stanford, California, United States
NorthwesternU
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
Tufts Medical Center
Boston, Massachusetts, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Memorial Sloan- Kettering Cancer Center
New York, New York, United States
MD Anderson Cancer Center
Houston, Texas, United States
Complete Remission Rate After Chemotherapy
The primary objective of this study is to evaluate the complete remission rate among older patients with HL receiving sequential brentuximab vedotin therapy with AVD chemotherapy
Time frame: after completion of AVD chemotherapy and prior to SGN-35 consolidation, approximately 9 months
Overall Response Rate After 2 Cycles of SGN-35
The incidence of overall response rate to induction SGN-35 will be reported for the initial 22 patients where PET is being employed.
Time frame: 2 cycles of SGN-35 lead-in therapy, approximately 42 days
Complete Remission Rate Following 2 Cycles of SGN-35
The incidence of CR rate to induction SGN-35 will be reported for the initial 22 patients where PET is being employed
Time frame: 2 cycles of lead-in SGN-35, approximately 42 days
Safety of Sequential SGN-35/AVD/SGN-35 Therapy
Detailed examination of Averse Events, laboratory test results, vital signs or other physical findings. Below we have summarized the top 10 most common Grade 3 and Grade 4 related adverse events. Please see the Adverse Events section of this record for a full listing of Adverse Events.
Time frame: From time of treatment to 30 days after discontinuation of study treatment
2-year Progression Free Survival
Progression Free Survival (PFS) is defined as lymphoma progression or death from any cause. This outcome measure is the percentage of patients that have not progressed at 2 years from time of registration.
Time frame: 2 years from time of registration to study
Overall Survival Following SGN-35/AVD Sequential Therapy
Defined as the percentage of patients that are alive 2 years after registration.
Time frame: up to 2 years from the time of registration
2 Year Event-Free Survival
An event is defined as treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death. This outcome measure is reported as the percentage of patient that did not have an event at 2 years from registration.
Time frame: From registration until treatment failure, up to 2 years
Freedom From Progression
Measured from the time of study entry to progression of disease. Other causes of treatment failure are not include in freedom from progression.
Time frame: from baseline to end of study, approximately 4 years
Patient Reported Outcomes for Symptoms and Quality of Life
Evaluate patient reported outcomes at baseline and during treatment to determine potential symptom palliation, treatment-related symptoms, and overall health-related quality of life. The Function Assessment of Cancer Therapy for Lymphoma (FACT-Lym) scale has a range of 0(minimum score) to 168 (maximum score). Higher scores indicate a better outcome. The mean scores for each timepoint are reported below.
Time frame: Baseline and AVD Cycle 1, a total of 6 weeks
Association Between Cumulative Illness Rating Scale (CIRS) With Outcomes
Number of co-morbidities collected for each patient at baseline and at the end of completion of all therapy utilizing the Cumulative Illness Rating Scare (CIRS). For binary outcomes such as CR, logistic regression will be used to assess the relationship with CIRS score; for time-to-event outcomes, the method of Kalan Meier and the log rank test will be used. The minimum score of the CIRS is 0 and the maximum score is 56. High Scores on the CIRS scale indicate that the patient has more severe comorbidities
Time frame: approximately 2 years from treatment start
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