Clinical trial NCT02758717: Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ann Arbor Stage IB Hodgkin Lymphoma
Ann Arbor Stage II Hodgkin Lymphoma
Ann Arbor Stage IIA Hodgkin Lymphoma
Ann Arbor Stage IIB Hodgkin Lymphoma
Ann Arbor Stage III Hodgkin Lymphoma
Ann Arbor Stage IIIA Hodgkin Lymphoma
Ann Arbor Stage IIIB Hodgkin Lymphoma
Ann Arbor Stage IV Hodgkin Lymphoma
Ann Arbor Stage IVA Hodgkin Lymphoma
Ann Arbor Stage IVB Hodgkin Lymphoma
Classic Hodgkin Lymphoma
Lead sponsor: Academic and Community Cancer Research United
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-05-02
Enrollment: 46
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. 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. 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.

Detailed description: PRIMARY OBJECTIVE:

I. To determine the efficacy based on overall metabolic response rate (partial metabolic response \[PMR\] + complete metabolic remission \[CMR\]) 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 complete metabolic response (CMR) rate. 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).

CORRELATIVE RESEARCH 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 cycles and 6-8 weeks in cycle 8 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 30 days for 90 days, every 90 days for 2.5 years, and then every 6 months until 5 years from registration.

Eligibility criteria: Inclusion Criteria:

* Classical Hodgkin lymphoma determined by local hematopathology review
* One of the following:

  * Age \>= 60 years
  * Age \< 60 years but unsuitable for standard chemotherapy because of a cardiac ejection fraction of \< 50%, a pulmonary diffusion capacity \< 80%, or a creatinine clearance \>= 30 and \< 60 mL/min, or refused standard chemotherapy despite efforts to convince them otherwise
* 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, unless secondary to bone marrow involvement; obtained =\< 7 days prior to registration
* Leukocytes \>= 3,000/mm\^3, obtained =\< 7 days prior to registration
* Platelet count \>= 100,000/mm\^3, obtained =\< 7 days prior to registration
* Hemoglobin \> 9.0 g/dL - unless determined by treating physician to be disease related, obtained =\< 7 days prior to registration
* Total bilirubin =\< 1.5 x upper limit of normal (ULN), obtained =\< 7 days prior to registration
* Aspartate aminotransferase (aspartate transaminase \[AST\]) =\< 2.5 x ULN, obtained =\< 7 days prior to registration
* Alanine aminotransferase (alanine transaminase \[ALT\]) =\< 2.5 x ULN, obtained =\< 7 days prior to registration
* Creatinine =\< 2.0 mg/dL, obtained =\< 7 days prior to registration
* Amylase and/or lipase =\< 1.5 x ULN, obtained =\< 7 days prior to registration
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) 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 (i.e., 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 antibody \[Ab\]+ then polymerase chain reaction \[PCR\]+) indicating acute or chronic infection, and/or history of 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
* Known history of pancreatitis

Primary outcomes:
measure: Overall Metabolic Response Rate
timeFrame: Up to 8 cycles of treatment (approximately 29 weeks)
Secondary outcomes:
measure: Number of Participants With an Overall Response of Complete Metabolic Response
timeFrame: Up to end of course 8
measure: Duration of Response (DOR)
timeFrame: 30 months
measure: Progression-free Survival
timeFrame: 30 months
measure: Overall Survival
timeFrame: 30 months
measure: Number of Participants Experiencing at Least One Adverse Events Graded 3 or Higher Deemed at Least Possibly Related to Treatment
timeFrame: Up to 8 cycles of treatment (approximately 29 weeks)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Institute Palo Alto
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: Academic and Community Cancer Research United
name: Bruce D Cheson
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cheson BD, Bartlett NL, LaPlant B, Lee HJ, Advani RJ, Christian B, Diefenbach CS, Feldman TA, Ansell SM. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2020 Nov;7(11):e808-e815. doi: 10.1016/S2352-3026(20)30275-1. Epub 2020 Oct 1.