Phase II Study of PET-Directed Frontline Therapy With Pembrolizumab and AVD for Patients With Classical Hodgkin Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Computed Tomography
- Conditions
- Classical Hodgkin Lymphoma
- Sponsor
- Northwestern University
- Enrollment
- 30
- Locations
- 4
- Primary Endpoint
- Complete Response (CR) With Pembrolizumab Treatment Alone
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Jane N. Winter
Principal Investigator
Northwestern University
Eligibility Criteria
Inclusion Criteria
- •Patients must have a histologically confirmed diagnosis of classical Hodgkin lymphoma including nodular sclerosis, mixed cellularity, lymphocytic-rich, and lymphocyte depleted subtypes by the 4th edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues published in 2008 (nodular lymphocyte-predominant Hodgkin lymphoma \[NLPHL\] excluded)
- •Patients must have measurable disease by the Lugano criteria
- •Patients must have previously untreated disease (except for one week or less of corticosteroids)
- •Patients must exhibit a/an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Patients may have any stage and any International Prognostic Score (IPS)
- •Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
- •Leukocytes \>= 3,000/mcL
- •Absolute neutrophil count \>= 1,500/mcL
- •Platelets \>= 100,000/mcl
- •Total bilirubin within normal institutional limits
Exclusion Criteria
- •Patients are not eligible who have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to registration or who have not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
- •NOTE: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- •NOTE: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- •Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration are not eligible
- •Patients who have a known history of active TB (bacillus tuberculosis) are not eligible
- •Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab
- •Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
Arms & Interventions
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Computed Tomography
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Dacarbazine
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Doxorubicin Hydrochloride
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Fludeoxyglucose F-18
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Laboratory Biomarker Analysis
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Pembrolizumab
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Positron Emission Tomography
Treatment (FDG-PET/CT, pembrolizumab, chemotherapy)
See Detailed Description
Intervention: Vinblastine Sulfate
Outcomes
Primary Outcomes
Complete Response (CR) With Pembrolizumab Treatment Alone
Time Frame: After 3 cycles of pembrolizumab (1 cycle = 21 days)
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.
Secondary Outcomes
- PFS for Elderly Patients(Up to 2 years)
- Overall Survival (OS) for Patients <60(Up to 2 years)
- OS for Elderly Patients(Up to 2 years)
- Progression Free Survival (PFS) for Patients <60(Up to 2 years)
- Incidence of Adverse Events(Up to 2 years)
- FDG Uptake(Up to 4 weeks after last dose of chemotherapy)