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About
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.
Full 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.
Enrollment
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Inclusion criteria
NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Has not undergone a hysterectomy or bilateral oophorectomy
Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
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
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:
Patients who have a known additional malignancy that is progressing or requires active treatment are not eligible
Patients who have known active central nervous system (CNS) metastases and/or carcinomatous meningitis are not eligible
Patients who have active autoimmune disease that has required systemic treatment in the past 2 years are not eligible (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
Patients who have known history of, or any evidence of active, non-infectious pneumonitis are not eligible
Patients who have an active infection requiring systemic therapy are not eligible, except for uncomplicated urinary tract infections
Patients are not eligible who have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Patients who have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial are not eligible
Patients may not be pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, from registration through 120 days after the last dose of trial treatment
Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent are not eligible
Patients who have a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) are not eligible
Patients who have active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis c virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) are not eligible
Patients who received a live vaccine within 30 days of planned start of study therapy are not eligible; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid vaccine
Primary purpose
Allocation
Interventional model
Masking
30 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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