RECRUITING

Brentuximab Vedotin and Nivolumab for the Treatment of Patients with Relapsed/refractory Classical Hodgkin Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

A Phase 2 Study of Brentuximab Vedotin Plus Nivolumab Without Stem Cell Consolidation in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma

Quick Facts

Study Start:2021-11-12

Study Completion:2026-10-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04561206

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Documented informed consent of the participant and/or legally authorized representative * 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) approval * 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. * 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 formula * 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 therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)	* 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 nivolumab * 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 feasibility/logistics)

Inclusion Criteria

Exclusion Criteria

* Documented informed consent of the participant and/or legally authorized representative
* 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) approval
* 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.
* 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 formula
* 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 therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

* 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 nivolumab
* 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 feasibility/logistics)

Contacts and Locations

Study Contact

Alex Herrera, MD

CONTACT

626-359-8111

aherrera@coh.org

Principal Investigator

Alex F Herrera

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

University of Chicago Cancer Research Center

Chicago, Illinois, 60637

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Hackensack University Medical Center/John Theurer Cancer Center

Hackensack, New Jersey, 07601

United States

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

Alex F Herrera, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-11-12

Study Completion Date2026-10-02

Study Record Updates

Study Start Date2021-11-12

Study Completion Date2026-10-02

Terms related to this study

Additional Relevant MeSH Terms

Relapsed Classic Hodgkin Lymphoma