Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Nivolumab and Brentuximab Vedotin in Treating Older Patients with Untreated Hodgkin Lymphoma

Protocol: OSU-15239

Full Title

Phase II, Multi-center Trial of Nivolumab and Brentuximab Vedotin in Patients with Untreated Hodgkin Lymphoma Over the Age of 60 Years or Unable to Receive Standard Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) Chemotherapy

Purpose

This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.

Study Objective

PRIMARY OBJECTIVES:

I. To determine the efficacy based on complete metabolic remission (CMR) rate of brentuximab vedotin/nivolumab in previously untreated Hodgkin lymphoma patients 60 years of age or older, or those considered unsuitable for standard chemotherapy because of a low cardiac ejection fraction (<50%) or impaired pulmonary or renal function.

SECONDARY OBJECTIVES:

I. The overall response rate (CMR + partial metabolic response [PMR]).

II. Safety and tolerability of the regimen in this patient population.

III. Duration of response (DOR).

IV. Progression-free survival (PFS).

V. Overall survival (OS).

TERTIARY OBJECTIVES:

I. T-cell/cytokine - peripheral blood specimens will be used to assess T-cell activation and cytokine up regulation as measures of treatment effect.

II. Biomarkers - intratumoral cell populations, genetic variability, serum cytokines and T-cell activation will be evaluated to identify potential biomarkers that correlate with response to therapy.

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 7 courses and 6-8 weeks in course 8 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, 90, 150, 210, 270 days, every 90 days for 2 years, and then every 6 months for 5 years.

Are you eligible?

Inclusion Criteria:

Classical Hodgkin lymphoma determined by local hematopathology review

One of the following:

Age >= 60 years

Patients =< 60 years that are unsuitable for, or refused, standard chemotherapy because of a cardiac ejection fraction of < 50%, a pulmonary diffusion capacity < 80%, or a creatinine clearance < 30 mL/min

Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if involved field is considered radiotherapy (RT) curative

Previously untreated with either chemotherapy, radiation therapy or either brentuximab vedotin or nivolumab, or another check point inhibitor

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

Absolute neutrophil count (ANC) >= 1500/mm^3

Leukocytes >= 3,000/mm^3

Platelet count >= 100,000/mm^3

Hemoglobin > 9.0 g/dL

Total bilirubin =< 1.5 x upper limit of normal (ULN)

Aspartate transaminase (AST) =< 2.5 x ULN

Alanine transaminase (ALT) =< 2.5 x ULN

Creatinine =< 2.0 mg/dL

Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to registration; Note: women of child-bearing potential (WOCBP) must use appropriate method(s) of contraception; WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug; men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study); Note: During the Active Monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up

Ability to understand and willingness to sign an informed written consent

Provide blood and tissue samples for mandatory correlative research purposes

Exclusion Criteria:

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown

Pregnant women

Nursing women

Men or women of childbearing potential who are unwilling to employ adequate contraception

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Active, known or suspected autoimmune disease; Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger

Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications =< 14 days of registration; Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

Immunocompromised patients, patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and currently receiving antiretroviral therapy, patients with a prior history of known or suspected autoimmune disease, active Hepatitis B virus surface antigen (HBV sAg+), active Hepatitis C (if Ab+ then PCR+) indicating acute or chronic infection, a history of pancreatitis and/or interstitial lung disease

Allergy to brentuximab vedotin and/or nivolumab

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

Have had prior chemotherapy or radiotherapy for Hodgkin lymphoma

Have received either of the study drugs

< 60 years who are considered candidates for standard chemotherapy

>= grade 2 peripheral neuropathy

Other active malignancy =< 2 years prior to registration, unless treated with curative intent; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer

Active central nervous system (CNS) involvement or leptomeningeal metastases involvement