A Phase 2 study of Brentuximab Vedotin plus Nivolumab without Stem Cell Consolidation in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma

Protocol # :
Relapsed Classic Hodgkin Lymphoma
Disease Sites
Hodgkin's Lymphoma
Principal Investigator
Armand, Philippe
Site Research Nurses
Aiken, Haley
Aiken, Haley
Chung, Anita
Maciejewski, Ashley, Taylor
Smith, Caitlin
Tichon, Jennifer

Trial Description

This phase II trial investigates how well brentuximab vedotin and nivolumab work in treating
patients with classical Hodgkin lymphoma that has come back after initial treatment
(relapsed) or has not responded to initial treatment (refractory). 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.
Nivolumab is an antibody that enhances the immune system to better fight Hodgkin lymphoma
cells. Giving brentuximab vedotin and nivolumab may be able to defer stem cell transplant
treatment and spare the considerable cost and toxicity on transplantation.

Eligibility Requirements

Inclusion Criteria:

- Documented informed consent of the participant and/or legally authorized

- Assent, when appropriate, will be obtained per institutional guidelines

- Be willing to provide tissue (either from a fresh core or excisional biopsy performed
as standard of care, or from archival tissue) of a biopsy that was performed after
frontline systemic therapy, and prior to starting protocol therapy

- If unavailable, exceptions may be granted with study principal investigator (PI)

- Eastern Cooperative Oncology Group (ECOG) =< 2

- Histologically confirmed diagnosis of classical Hodgkin lymphoma (excluding nodular
lymphocyte predominant Hodgkin lymphoma) according to the World Health Organization
(WHO) classification, with hematopathology review at the participating institution

- Relapsed or refractory disease after no more than 1 line of prior therapy (not
counting radiotherapy). However, a maximum of 5 patients with primary refractory
disease may be enrolled in this study.

Note: Patients who received BV or an anti-PD-1/PD-L1 agent as part of frontline therapy are
eligible if they achieved a CMR with frontline therapy and have not relapsed within 6
months from the end of frontline therapy Relapse must have been confirmed histologically
(with hematopathology review at the participating institution)

- Not a candidate for ASCT, based on age, co-morbidities, or patient preference. The
reason for ASCT non-candidacy must be documented in the Case Report Form and verified
by the site PI

- Measurable disease (at least one non-bony fludeoxyglucose F-18 [FDG]-avid lesion >=
1.5 cm in long axis)

- Absolute neutrophil count (ANC) >= 1,000/mm^3

- NOTE: Growth factor is not permitted within 7 days of ANC assessment unless
cytopenia is secondary to disease involvement

- Platelets >= 50,000/mm^3

- NOTE: Platelet transfusions are not permitted within 7 days of platelet
assessment unless cytopenia is secondary to disease involvement

- Hemoglobin >= 8 g/dL (no transfusion allowed within 3 days prior to screening)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< 1.5 x ULN
for patients with Gilbert's disease

- Aspartate aminotransferase (AST) =< 2.5 x ULN

- Alanine aminotransferase (ALT) =< 2.5 x ULN

- Creatinine clearance of >= 40 mL/min per 24 hour urine test or the Cockcroft-Gault

- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required

- Agreement by women and men of childbearing potential* to use an effective method of
birth control or abstain from heterosexual activity for the course of the study
through at least 5 months (women) or 7 months (men) after the last dose of protocol

- Childbearing potential defined as not being surgically sterilized (men and women)
or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

- Concomitant investigational therapy

- Live vaccine within 30 days prior to day 1 of protocol therapy (e.g. measles, mumps,
rubella, varicella, yellow fever, rabies, bacillus Calmette-Guerin [BCG], oral polio
vaccine, and oral typhoid)

- Grade >= 2 peripheral neuropathy

- History of prior >= grade 3 hypersensitivity to either brentuximab vedotin or

- Known active central nervous system (CNS) involvement by lymphoma, including
parenchymal and/or lymphomatous meningitis

- History of another primary malignancy that has not been in remission for at least 3
years, with the following exceptions:

- Non-melanoma skin cancer treated with curative intent

- In situ cervical cancer

- If the malignancy is expected to not require any treatment for at least 2 years
(this exception should be discussed with the study PI)

- Condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone or equivalent) or other immunosuppressive medications within 14 days of
study drug administration. Exceptions are:

- Inhaled or topical steroids and

- Adrenal replacement doses > 10 mg daily prednisone equivalents in the absence of
active autoimmune disease

- History of progressive multifocal leukoencephalopathy (PML)

- Prior diagnosis of inherited or acquired immunodeficiency

- Active pneumonitis or interstitial lung disease

- Active, known or suspected autoimmune disease. The following are exceptions:

- Vitiligo

- Psoriasis not requiring systemic treatment

- Hemolytic anemia associated with the lymphoma

- Type I diabetes mellitus, if adequately controlled with therapy

- Thyroid disease, if adequately controlled with therapy

- Conditions not expected to recur in the absence of an external trigger (such
exceptions should be discussed with the study PI)

- Active history of:

- Hepatitis B (hepatitis B virus [HBV]) or C (hepatitis C virus [HCV]) infection.
Patients with past HBV infection (defined as negative hepatitis B surface antigen
[HBsAg] and positive hepatitis B core antibody [HBcAb]) are eligible if HBV DNA
is undetectable. Patients who are positive for HCV antibody are eligible if
polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)

- Human immunodeficiency virus (HIV) infection. Subjects who have an undetectable
or unquantifiable human immunodeficiency virus (HIV) viral load with CD4 >= 200
and are on highly active antiretroviral therapy (HAART) medication are allowed.
Testing to be done only in patients suspected of having infections or exposures

- History of a cerebral vascular event (stroke or transient ischemic attack), unstable
angina, myocardial infarction, or cardiac symptoms consistent with New York Heart
Association class III-IV within 6 months prior to day 1 of protocol therapy

- Pregnant or breastfeeding

- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures

- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to