The purpose of this research study is to evaluate a new drug pembrolizumab in combination with chemotherapy, for the treatment of newly diagnosed Hodgkin lymphoma. The chemotherapy regimen is called AVD and includes three drugs: adriamycin, vinblastin, dacarbazine. Pembrolizumab is currently FDA approved for the treatment of some patients with melanoma, lung cancer and head and neck cancer, but has not yet been approved for the treatment of Hodgkins Lymphoma. The AVD regimen of chemotherapy is currently FDA approved for the treatment of newly diagnosed Hodgkin lymphoma, but has not yet been investigated in combination with pembrolizumab for this disease. For patients who have a new diagnosis of Hodgkins Lymphoma, multi-agent chemotherapy is recommended. Also, for patients who do not have a complete response to chemotherapy (meaning there is still evidence of disease on PET scans performed at the end of treatment), radiation is sometimes recommended. Furthermore, the rare patient who relapses after chemotherapy requires treatment with high dose chemotherapy and a transplant.
PRIMARY OBJECTIVES: I. Assess the percent of patients who achieve a complete response (CR) to single-agent pembrolizumab induction, among patients with classical Hodgkin lymphoma (cHL) using Lugano 2014 criteria., as measured at PET #2. SECONDARY OBJECTIVES: I. Assess the safety and tolerability of pembrolizumab in combination with chemotherapy in the frontline setting. II. Determine the three-year progression free survival (PFS) and overall survival (OS) for patients \< 60 with early non-bulky disease, and elderly patients (all stages) treated with pembrolizumab with doxorubicin hydrochloride (Adriamycin), (bleomycin), vinblastine sulfate, dacarbazine (A\[B\]VD) in the frontline treatment of patients with cHL. III. Determine the extent of fludeoxyglucose F-18 (FDG) uptake, using a semi-quantitative approach (e.g., Deauville score), after pembrolizumab induction, and after subsequent chemotherapy. TERTIARY OBJECTIVES: I. To characterize PD-1 pathway specific expression and correlate with response. II. To characterize serum biomarkers of immune and inflammatory response during treatment. III. To characterize levels of soluble PD-L1 related to treatment with pembrolizumab. IV. To characterize T-lymphocyte subset changes to treatment with pembrolizumab. V. To investigate the prevalence and clinical correlation of chromosome 9p24.1 alterations for this population. OUTLINE: INITIATION: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/computed tomography (CT) scans before the start of pembrolizumab and after 3 courses. AVD: Within 21 days after final dose of pembrolizumab, patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a final FDG-PET/CT scan on day 117-120 or 26-29 of course 2. Patients with stage I/II disease with a CR continue treatment for up to 2 courses. Patients with stage III/IV disease with a CR or age \>= 60 with stage III/IV disease with any response continue treatment for up to 4 courses. CONSOLIDATION: Patients age \>= 60 with stage III/IV disease who received \< 6 courses of AVD or patients age \>= 60 with DV 4-5 on FDG-PECT/CT scan receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Undergo FDG-PET/CT
Given IV
Given IV
Undergo FDG-PET/CT
Correlative studies
Given IV
Undergo FDG-PET/CT
Given IV
Stanford Cancer Institute
Stanford, California, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
Rutgers Cancer Institute
New Brunswick, New Jersey, United States
Complete Response (CR) With Pembrolizumab Treatment Alone
To assess the primary objective of response rate following PET #2 performed after 3 doses of pembrolizumab. PET response will be assessed using the Lugano Criteria (2014) which recommends the 5 point Deauville score for assessing response. The Deauville five-point scale is an internationally-recommended scale for routine clinical reporting and clinical trials using FDG PET-CT in the initial staging and assessment of treatment response in Hodgkin lymphoma (HL). Patients with a Deauville score of 1-3 will be considered a complete response. Deauville criteria is defined as follows: 1. No residual uptake 2. Slight uptake, but below blood pool (mediastinum) 3. Uptake above mediastinum, but below or equal to uptake in the liver 4. Uptake slightly to moderately higher than liver 5. Markedly increased uptake or any new lesions Patients will be evaluable for response assessment if they have received at least one dose of pembrolizumab.
Time frame: After 3 cycles of pembrolizumab (1 cycle = 21 days)
Incidence of Adverse Events
To assess safety and tolerability, all adverse events will be summarized in terms of type, grade, timing and attribution to treatment and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE version 4.03).
Time frame: Up to 2 years
Progression Free Survival (PFS) for Patients <60
PFS for patients \<60 will be measured.
Time frame: Up to 2 years
PFS for Elderly Patients
PFS for elderly patients will be measured.
Time frame: Up to 2 years
Overall Survival (OS) for Patients <60
OS for patients \<60 will be evaluated.
Time frame: Up to 2 years
OS for Elderly Patients
OS for elderly patients will be evaluated.
Time frame: Up to 2 years
FDG Uptake
Evaluate the extent of FDG uptake by assessing PET scans to determine a Deauville score.
Time frame: Up to 4 weeks after last dose of chemotherapy
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