PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

Classical Hodgkin Lymphoma Clinical Trial

Official title: Phase II Study of PET-Directed Frontline Therapy With Pembrolizumab and AVD for Patients With Classical Hodgkin Lymphoma

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Classical Hodgkin Lymphoma
• Hodgkin Disease
• Lymphocyte-Depleted Classical Hodgkin Lymphoma
• Lymphocyte-Rich Classical Hodgkin Lymphoma
• Lymphoma
• Mixed Cellularity Classical Hodgkin Lymphoma
• Nodular Sclerosis Classical Hodgkin Lymphoma

• NCT number: NCT03226249
• Study type: Interventional
• Source: Northwestern University
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 9, 2017
• Completion date: October 2024