RECRUITING

Brentuximab Vedotin and Nivolumab for the Treatment of Relapsed/Refractory Classic Hodgkin Lymphoma Previously Treated With Brentuximab Vedotin or Checkpoint Inhibitors

Conditions

Recurrent Classic Hodgkin Lymphoma Refractory Classic 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 studies the effect of brentuximab vedotin and nivolumab in treating patients with classic Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory) that have been previously treated with brentuximab vedotin or checkpoint inhibitors. 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. 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. Giving brentuximab vedotin and nivolumab in combination may be an effective treatment in patients with relapsed or refractory classic Hodgkin lymphoma previously treated with brentuximab vedotin or checkpoint inhibitors.

Official Title

A Phase 2 Study of Brentuximab Vedotin Plus Nivolumab in Patients With Relapsed/Refractory Hodgkin Lymphoma Previously Treated With Brentuximab or Checkpoint Inhibitors

Quick Facts

Study Start:2022-05-02

Study Completion:2027-11-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05039073

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:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically confirmed classical Hodgkin lymphoma * Patients must be 12 years of age or older * Patients must have received at least 1-2 prior multi-agent chemotherapy or immunotherapy regimens will be divided into two cohorts based on the following clinical scenarios: * Patients enrolled to cohort A must have received only ONE prior brentuximab-containing regimen with NO prior checkpoint inhibitors. Patients enrolled to cohort A must have received brentuximab as part of their first-line treatment regimen. * Patients enrolled to cohort B must have received only ONE prior immune checkpoint inhibitor- (i.e. nivolumab or pembrolizumab) containing regimen and NO prior brentuximab. Patients in cohort B may have received an immune checkpoint inhibitor during either their first- or second-line treatment regimen. * If radiation is used as part of the planned front-line treatment regimen (i.e., brentuximab vedotin-doxorubicin-vinblastine-dacarbazine \[BV-AVD\] + radiation therapy \[RT\] for bulky stage II disease), this will count as only 1 prior therapy. Additionally, radiation as consolidation after a second-line multi-agent chemotherapy regimen is permitted and will not be counted as a third regimen * No prior autologous or allogeneic transplant * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 for patients \> 18 years old, or Lansky performance status of \>= 50 for patients ages 12-18 years * Enrolling patients must have measurable disease defined as a tumor or nodal mass \> 1.5 cm in at least one dimension * Resolution of all prior toxicities, including peripheral neuropathy, to a =\< grade 1 * Absolute neutrophil count (ANC) \>= 750, unless disease related (within 28 days of cycle 1 day 1) * Platelets \>= 50,000, unless disease related (within 28 days of cycle 1 day 1) * Creatinine =\< upper limit of normal (ULN) (within 28 days of cycle 1 day 1) * Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =\< 3 x ULN (within 28 days of cycle 1 day 1) * Bilirubin =\< 2 mg/dL (within 28 days of cycle 1 day 1) * Patients with human immunodeficiency virus (HIV) infection are eligible. Patients with HIV infection must meet the following criteria: No evidence of co-infection with hepatitis B or C; CD4+ count \>= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load \< 50 copies HIV ribonucleic acid (RNA)/mL. Patients with HIV must have ongoing follow-up with an infectious disease specialist and must have been evaluated within 90 days of cycle 1 day 1. * Females of child-bearing potential (FCBP) must have a negative urine pregnancy test prior to starting therapy. If the test is positive, pregnancy must be ruled out * FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation, and 6 months after completion of brentuximab and/or nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * A female of childbearing potential (FCBP) is a post-menarcheal woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months * Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer \>= 2 weeks before the start of study therapy * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better * Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions * Evidence of a personally signed informed consent by patients \>= 18 year old (YO) or parent or legally authorized representative (LAR) for patients 12-17 YO indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation. Patients 12-17 will also be required to give assent to the process per institutional guidelines	* Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for \>= 2 years or which will not limit survival to \< 2 years * Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events to =\< grade 1 * Active autoimmune disease or history of autoimmune disease such as hepatitis, hypophysitis, nephritis, interstitial lung disease, and colitis * Active central nervous system (CNS) involvement with lymphoma * Patients with hepatitis B (positive hepatitis B virus surface antigen \[HBsAg\] or hepatitis B virus core antibody \[HBcAb\]) and those with positive hepatitis C virus (HCV) antibodies are not permitted to enroll * No active infection, or other active 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

Inclusion Criteria

Exclusion Criteria

* Histologically confirmed classical Hodgkin lymphoma
* Patients must be 12 years of age or older
* Patients must have received at least 1-2 prior multi-agent chemotherapy or immunotherapy regimens will be divided into two cohorts based on the following clinical scenarios:
* Patients enrolled to cohort A must have received only ONE prior brentuximab-containing regimen with NO prior checkpoint inhibitors. Patients enrolled to cohort A must have received brentuximab as part of their first-line treatment regimen.
* Patients enrolled to cohort B must have received only ONE prior immune checkpoint inhibitor- (i.e. nivolumab or pembrolizumab) containing regimen and NO prior brentuximab. Patients in cohort B may have received an immune checkpoint inhibitor during either their first- or second-line treatment regimen.
* If radiation is used as part of the planned front-line treatment regimen (i.e., brentuximab vedotin-doxorubicin-vinblastine-dacarbazine \[BV-AVD\] + radiation therapy \[RT\] for bulky stage II disease), this will count as only 1 prior therapy. Additionally, radiation as consolidation after a second-line multi-agent chemotherapy regimen is permitted and will not be counted as a third regimen
* No prior autologous or allogeneic transplant
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 for patients \> 18 years old, or Lansky performance status of \>= 50 for patients ages 12-18 years
* Enrolling patients must have measurable disease defined as a tumor or nodal mass \> 1.5 cm in at least one dimension
* Resolution of all prior toxicities, including peripheral neuropathy, to a =\< grade 1
* Absolute neutrophil count (ANC) \>= 750, unless disease related (within 28 days of cycle 1 day 1)
* Platelets \>= 50,000, unless disease related (within 28 days of cycle 1 day 1)
* Creatinine =\< upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
* Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =\< 3 x ULN (within 28 days of cycle 1 day 1)
* Bilirubin =\< 2 mg/dL (within 28 days of cycle 1 day 1)
* Patients with human immunodeficiency virus (HIV) infection are eligible. Patients with HIV infection must meet the following criteria: No evidence of co-infection with hepatitis B or C; CD4+ count \>= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load \< 50 copies HIV ribonucleic acid (RNA)/mL. Patients with HIV must have ongoing follow-up with an infectious disease specialist and must have been evaluated within 90 days of cycle 1 day 1.
* Females of child-bearing potential (FCBP) must have a negative urine pregnancy test prior to starting therapy. If the test is positive, pregnancy must be ruled out
* FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation, and 6 months after completion of brentuximab and/or nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* A female of childbearing potential (FCBP) is a post-menarcheal woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months
* Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer \>= 2 weeks before the start of study therapy
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
* Evidence of a personally signed informed consent by patients \>= 18 year old (YO) or parent or legally authorized representative (LAR) for patients 12-17 YO indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation. Patients 12-17 will also be required to give assent to the process per institutional guidelines

* Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for \>= 2 years or which will not limit survival to \< 2 years
* Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events to =\< grade 1
* Active autoimmune disease or history of autoimmune disease such as hepatitis, hypophysitis, nephritis, interstitial lung disease, and colitis
* Active central nervous system (CNS) involvement with lymphoma
* Patients with hepatitis B (positive hepatitis B virus surface antigen \[HBsAg\] or hepatitis B virus core antibody \[HBcAb\]) and those with positive hepatitis C virus (HCV) antibodies are not permitted to enroll
* No active infection, or other active 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

Contacts and Locations

Principal Investigator

Jason T Romancik, MD

PRINCIPAL_INVESTIGATOR

Emory University Hospital/Winship Cancer Institute

Study Locations (Sites)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342

United States

Collaborators and Investigators

Sponsor: Emory University

Jason T Romancik, MD, PRINCIPAL_INVESTIGATOR, Emory University Hospital/Winship Cancer Institute

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 Date2022-05-02

Study Completion Date2027-11-30

Study Record Updates

Study Start Date2022-05-02

Study Completion Date2027-11-30

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Classic Hodgkin Lymphoma
Refractory Classic Hodgkin Lymphoma