Brentuximab Vedotin and Nivolumab in Treating Patients with Early Stage Classic Hodgkin Lymphoma

Status: Active

Description

This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin and nivolumab, may interfere with the ability of tumor cells to grow and spread.

Eligibility Criteria

Inclusion Criteria

  • Documented informed consent of the participant and/or legally authorized representative. * Assent, when appropriate, will be obtained per institutional guidelines.
  • 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.
  • Stage IA, IB, IIA, or IIB cHL by Cotswold modified Ann Arbor staging done prior to any treatment with ABVD.
  • Ability to document transverse diameter in cm of largest mediastinal mass and favorable versus unfavorable risk factor criteria as determined by German Hodgkin Study Group (GHSG) criteria at baseline prior to ABVD treatment.
  • Must have at baseline prior to ABVD treatment at least one lesion that is > 1.5 cm in the longest diameter on cross‐sectional imaging and measureable in two perpendicular dimensions on CT and fludeoxyglucose (FDG) avid by PET.
  • Absolute neutrophil count (ANC) >= 1,000/mm^3.
  • Platelets >= 75,000/mm^3.
  • Hemoglobin >= 8 g/dL.
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless the elevation is known to be related to Gilbert’s syndrome).
  • Aspartate aminotransferase (AST) =< 2.5 x ULN.
  • Alanine aminotransferase (ALT) =< 2.5 x ULN.
  • Creatinine clearance >= 30 mL/min per 24 hour urine collection or the Cockcroft‐Gault formula.
  • Left ventricular ejection fraction (LVEF) >= 45%.
  • Carbon monoxide diffusion capacity (DLCO) (adjusted for hemoglobin [Hb]) >= 60%.
  • 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 females and males 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 6 months after the last dose of protocol therapy. * 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

  • Patients must be naive in terms of any prior therapy for Hodgkin lymphoma (including immunotherapy, chemotherapy or radiation therapy) with the exception that they may have received up to 2 cycles of ABVD as standard of care therapy prior to enrollment, as long as they can start subsequent therapy (therapy administered in Arms A, B1/B2, or C) within timelines specified by the trial.
  • Subjects with a non‐lymphoma related condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drugs administration. Patients can have received short term dosing of steroids prior to the start of ABVD chemotherapy for management of symptoms of cHL and any steroids given for cHL symptom management should be tapered down to 10 mg or less of prednisone equivalents by the time of start of ABVD chemotherapy, and fully tapered off by week 1 of ABVD.
  • Sensory > grade 1 or any peripheral motor neuropathy.
  • History of another primary malignancy that has not been in remission for at least 3 years. (The following are exempt from the 3‐year limit: nonmelanoma skin cancer, fully excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolau [PAP] smear)
  • Known cerebral/meningeal disease.
  • History of progressive multifocal leukoencephalopathy (PML).
  • Known history of pancreatitis.
  • Documented 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 their first dose of study drug(s).
  • Uncontrolled cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 45%, coronary artery disease, or arrhythmias.
  • Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin, nivolumab, or any component of ABVD.
  • Known active infection with hepatitis B or hepatitis C. Patients who are hepatitis B carriers can enroll if have a negative hepatitis B polymerase chain reaction (PCR) DNA test and are on hepatitis B suppressive medication management with entecavir or lamivudine. Patients with past active hepatitis C virus (HCV) infection are eligible if they are PCR negative after curative therapy. Testing to be done only in patients suspected of having infections or exposures.
  • Known active infection with human immunodeficiency virus (HIV). Patients who are HIV positive can enroll if CD4 count is > 200/uL and have an undetectable HIV viral load within 28 days of enrollment, have concurrent management with infectious disease specialists, and are on stable combination antiretroviral therapy. Participants are required to be on antiretroviral regimens that are in accordance with the current International acquired immune deficiency syndrome (AIDS) Society guidelines concurrently with chemotherapy. The specific agents are at the discretion of the Investigator and the use of investigational agents currently available on an expanded access basis is allowed. Use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) or ritonavir (includes Norvir or Kaletra), Cobicistat, Didanosine (Videx or Videx EC), or similar potent CYP3 inhibitors are prohibited. In order to be eligible, participants taking zidovudine or ritonavir, Cobicistat, Didanosine, or other CYP3 inhibitors must change to a different regimen 7 days prior to therapy initiation. Changes to highly active antiretroviral therapy (HAART) therapy during the study may be made if medically necessary (toxicity, failure of regimen, etc.). Participants must be on HAART for at least 7 days prior to therapy.
  • Any active systemic viral, bacterial, or fungal infection requiring treatment with IV antimicrobial therapy within 1 week prior to enrollment.
  • Subjects with active interstitial pneumonitis.
  • Subjects with active, known or suspected autoimmune disease. Subjects with 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 are permitted to enroll.
  • Females only: 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 feasibility/logistics).

Locations & Contacts

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: In review
Contact: Andres Forero-Torres
Phone: 205-934-7167
Email: aforero@uabmc.edu

Arizona

Tucson
Banner University Medical Center - Tucson
Status: In review
Contact: Daniel O. Persky
Phone: 520-694-0111
Email: dpersky@uacc.arizona.edu

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Contact: Alex Francisco Herrera
Phone: 626-256-4673ext82405
Email: aherrera@coh.org
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: John Matthew Timmerman
Phone: 310-829-5471
Email: jtimmerman@mednet.ucla.edu
Palo Alto
Stanford Cancer Institute Palo Alto
Status: In review
Contact: Ranjana Hira Advani
Phone: 650-498-6000
Email: radvani@stanford.edu
San Diego
University of California San Diego
Status: In review
Contact: Carolyn Marie Mulroney
Phone: 858-822-6600
Email: camulroney@ucsd.edu

Colorado

Denver
Presbyterian - Saint Lukes Medical Center - Health One
Status: In review
Contact: Jeffrey Victor Matous
Phone: 720-754-4800
Email: jeffrey.matous@healthonecares.com
University of Colorado
Status: In review
Contact: Manali K. Kamdar
Phone: 720-848-3389
Email: manali.kamdar@ucdenver.edu

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: In review
Contact: Kristie A. Blum
Phone: 404-778-1900
Email: Kristie.a.blum@emory.edu

Illinois

Chicago
Northwestern University
Status: In review
Contact: Jane Norma Winter
Phone: 312-695-4538
Email: j-winter@northwestern.edu
University of Chicago Comprehensive Cancer Center
Status: In review
Contact: Sonali Mehta Smith
Phone: 773-834-2895
Email: smsmith@medicine.bsd.uchicago.edu

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: In review
Contact: Ann Steward LaCasce
Phone: 617-632-5959
Email: Ann_lacasce@dfci.harvard.edu
Charlestown
Massachusetts General Hospital
Status: In review
Contact: Jeremy S. Abramson
Phone: 617-724-4000
Email: jabramson@partners.org

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: In review
Contact: Radhakrishnan Ramchandren
Phone: 800-527-6266
Email: ramchanr@karmanos.org

Minnesota

Rochester
Mayo Clinic
Status: In review
Contact: Stephen Maxted Ansell
Phone: 507-284-2511
Email: ansell.stephen@mayo.edu

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: In review
Contact: Nancy L. Bartlett
Phone: 314-362-5654
Email: nbartlet@DOM.wustl.edu

New Jersey

Hackensack
Hackensack University Medical Center
Status: In review
Contact: Tatyana A. Feldman
Phone: 201-996-3033
Email: tfeldman@hackensackumc.org

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: In review
Contact: Catherine S. Magid Diefenbach
Phone: 404-778-1900
Email: catherine.diefenbach@nyumc.org
Memorial Sloan Kettering Cancer Center
Status: In review
Contact: Alison J. Moskowitz
Phone: 212-639-4839
Email: moskowia@mskcc.org
NYP / Weill Cornell Medical Center
Status: In review
Contact: Peter Martin
Phone: 646-962-2064
Email: pem9019@med.cornell.edu
Rochester
University of Rochester
Status: In review
Contact: Carla Casulo
Phone: 585-275-5823
Email: carla_casulo@urmc.rochester.edu

North Carolina

Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: In review
Contact: Steven I. Park
Phone: 704-403-1370
Email: Steven.park@carolinashealthcare.org

Ohio

Cleveland
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Status: In review
Contact: Deepa Jagadeesh
Phone: 216-444-0857
Email: jagaded@ccf.org

Oregon

Portland
Oregon Health and Science University
Status: In review
Contact: Andy I. Chen
Phone: 503-494-5058
Email: chenan@ohsu.edu

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: In review
Contact: Jakub Svoboda
Phone: 215-615-5858
Email: jakub.svoboda@uphs.upenn.edu

Tennessee

Nashville
Sarah Cannon Cancer Center
Status: In review
Contact: Ian Winchester Flinn
Phone: 615-986-7600
Email: iflinn@tnonc.com

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: In review
Contact: Martha J. Glenn
Phone: 801-585-0134
Email: martha.glenn@hci.utah.edu

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: In review
Contact: Ajay Kumar Gopal
Phone: 206-288-1000
Email: agopal@u.washington.edu

British Columbia

Vancouver
University of British Columbia Hospital
Status: In review
Contact: Kerry Joanne Savage
Phone: 604-877-6000
Email: ksavage@bccancer.bc.ca

Ontario

Toronto
University Health Network-Princess Margaret Hospital
Status: In review
Contact: John Kuruvilla
Phone: 416-946-4501
Email: john.kuruvilla@uhn.ca

Trial Objectives and Outline

PRIMARY OBJECTIVES:

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 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 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV 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 receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 courses 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 courses 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 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
City of Hope Comprehensive Cancer Center

Principal Investigator
Alex Francisco Herrera

Trial IDs

Primary ID 18157
Secondary IDs NCI-2018-01592
Clinicaltrials.gov ID NCT03712202