Brentuximab Vedotin and Nivolumab in Treating Patients with Early Stage Classic Hodgkin Lymphoma
16 Years and older, Male and Female
18157 (primary)
NCI-2018-01592
Summary
This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Objectives
PRIMARY OBJECTIVE:
I. Determine the 18-month progression free survival (PFS) for each arm of therapy stratified by positron emission tomography (PET)/computed tomography (CT)-2 response.
SECONDARY OBJECTIVES:
I. Assess safety, tolerability, and quality of life (QOL) for each arm of therapy.
II. Measure PET/CT-2 negativity rate after 2 lead-in cycles of standard of care doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD).
III. Evaluate the 3-year PFS and overall survival (OS) for each arm of treatment.
EXPLORATORY OBJECTIVES:
I. Evaluate if a baseline antitumor immune response, as assessed by a Nanostring gene panel, correlates with PFS.
II. Evaluate if minimal residual disease (MRD) status, as monitored by cancer personalized profiling by deep sequencing (CAPP-Seq) of circulating tumor (ct) deoxyribonucleic acid (DNA), can be correlated with PFS.
OUTLINE: Patients are assigned to 1 of 2 groups based on their PET/CT-2 scans.
GROUP I (PET/CT-2 NEGATIVE): Patients without bulky disease are randomized to either Arm A or B and patients with bulky disease are assigned to Arm B.
ARM A: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ARM B: (CLOSED) Patients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
GROUP II (PET/CT-2 POSITIVE): Patients receive doxorubicin IV, vinblastine IV, dacarbazine, IV and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients that are PET/CT negative receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 3 years.
Eligibility
- Documented informed consent of the participant and/or legally authorized representative.
* Assent, when appropriate, will be obtained per institutional guidelines.
- Be willing to provide archival tissue of a biopsy that was performed prior to standard of care ABVD treatment
* If unavailable, exceptions may be granted with study principal investigator (PI) approval.
- Age: >= 16 years
- Eastern Cooperative Oncology Group (ECOG) =< 2.
- Histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) by current World Health Organization classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, or classical Hodgkin lymphoma, NOS [not otherwise specified]) at local enrolling center. Nodular lymphocyte-predominant Hodgkin lymphoma is excluded
- Stage IA, IB, IIA, or IIB cHL by Cotswold modified Ann Arbor staging done prior to any treatment with ABVD.
- Must have prior to standard of care ABVD treatment at least one lesion that is > 1.5 cm in the longest diameter on cross-sectional imaging and measurable in two perpendicular dimensions on CT and fludeoxyglucose (FDG) avid by PET.
Treatment Sites in Georgia
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