ClinicalTrials.gg
RecruitingNCT04561206Updated Sep 22, 2026

Brentuximab Vedotin and Nivolumab for the Treatment of Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

A Phase 2 interventional study of Brentuximab Vedotin and Nivolumab in Relapsed Classic Hodgkin Lymphoma, sponsored by City of Hope Medical Center. Recruiting at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-22.

Sponsored by City of Hope Medical Center · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Nov 2021; still recruiting 4 years 11 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
31
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

PRIMARY OBJECTIVE:

I. Assess the durability of response to brentuximab vedotin (BV) plus nivolumab (nivo) by 24-month progression-free survival (PFS) in participants (with relapsed/refractory classical Hodgkin lymphoma (RcHL) after frontline therapy) who achieved early complete metabolic response (CMR) (CMR after 4 cycles).

SECONDARY OBJECTIVES:

I. Estimate CMR and overall response rate (ORR) after 4 cycles and at the end of BV-nivo therapy.

II. Estimate the PFS and overall survival (OS) for the entire cohort and for subgroups of patients defined by their response.

III. Estimate the PFS and OS separately for responders who did and did not receive radiotherapy.

IV. Evaluate the toxicities of BV-nivo in the study population.

EXPLORATORY OBJECTIVES:

I. Estimate the second PFS after salvage therapy for patients who progress after study therapy, and for the subset of these patients who proceeded to autologous stem cell transplant (ASCT).

II. Explore the association between clinical outcomes and pathological tumor characteristics.

III. Explore the association between clinical outcomes and circulating tumor deoxyribonucleic acid (ctDNA) characteristics (mutation profile, kinetics of clearance).

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and 6, 12, 18, 24, 36, 48, and 60 months.

02

Conditions studied

  • Relapsed Classic Hodgkin Lymphoma

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03

In context

Hodgkin Disease

1,383 studies on the registry are indexed under Hodgkin Disease; 163 are open to participants now.

This study's planned enrollment of 31 is below the median of 40 across 1,095 interventional studies indexed under Hodgkin Disease.

Browse Hodgkin Disease studies →

Lead sponsor

City of Hope Medical Center is the lead sponsor of 677 studies on the registry; 181 are open to participants now.

Of its 31 completed or terminated interventional studies of FDA-regulated products, 12 (39%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Documented 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 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
  • (ECOG) =\< 2
  • 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
  • disease after no more than 1 (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 /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 , 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
  • (at least one non-bony fludeoxyglucose F-18 [FDG]-avid lesion >= 1.5 cm in long axis)
  • (ANC) >= 1,000/mm\^3

    • NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
  • >= 50,000/mm\^3

    • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
  • >= 8 g/dL (no transfusion allowed within 3 days prior to screening)
  • Total =\< 1.5 x (ULN) or direct bilirubin =\< 1.5 x ULN for patients with Gilbert's disease
  • (AST) =\< 2.5 x ULN
  • Alanine aminotransferase (ALT) =\< 2.5 x ULN
  • of >= 40 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  • Women of (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 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)

Exclusion criteria

Exclusion Criteria:

  • Concomitant therapy
  • 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 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 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 (> 10 mg daily prednisone or equivalent) or other 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 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 virus [HBV]) or 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)
    • (HIV) infection. Subjects who have an undetectable or unquantifiable human immunodeficiency virus (HIV) viral load with >= 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 ), unstable angina, myocardial infarction, or cardiac symptoms consistent with 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)
Terms in these criteria, in plain language(31)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
31 participants (estimated)

Study arms

  • Experimental
    Treatment (brentuximab vedotin, nivolumab)

    Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

    Drug: Brentuximab Vedotin · Biological: Nivolumab

Interventions

  • Given IV

    Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

  • BiologicalNivolumab

    Given IV

    Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

06

What researchers measure

Primary outcomes

  1. Progression-free survival (PFS) at 24 months in patients who achieve complete metabolic response (CMR) after 4 cycles of treatment

    Estimated using Kaplan-Meier product limit method.

    Time frame: From start of protocol treatment to time of disease relapse/progression or death due to any cause, assessed at 24 months

Secondary outcomes

  1. Complete metabolic response (CMR) rate

    Defined as the proportion of response-evaluable participants that achieve a best response of CMR with brentuximab vedotin (BV)-nivolumab (Nivo) therapy. Will be estimated along with the 95% exact binomial confidence interval.

    Time frame: After 4 or 8 cycles (each cycle is 21 days)

  2. Overall response rate (ORR)

    defined as the proportion of response-evaluable participants that achieve a best response of either CMR or partial metabolic remission (PMR) with BV-Nivo therapy. Will be estimated along with the 95% exact binomial confidence interval.

    Time frame: After 4 or 8 cycles (each cycle is 21 days)

  3. Overall survival (OS)

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation. Median PFS/OS will be estimated when available. PFS and OS will be estimated for the entire cohort, for subgroups defined by response, and for responders who did and did not receive radiotherapy.

    Time frame: From start of protocol treatment to time of death due to any cause, assessed up to 5 years (each cycle is 21 days)

  4. PFS

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation. Median PFS/OS will be estimated when available. PFS and OS will be estimated for the entire cohort, for subgroups defined by response, and for responders who did and did not receive radiotherapy.

    Time frame: From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 5 years(each cycle is 21 days)

  5. Incidence of adverse events

    Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Observed toxicities of BV-Nivo therapy will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity, and attribution.

    Time frame: Up to 30 days post-treatment

07

Study locations

5 of 5 sites recruiting
08

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Nov 2021 (actual). Primary completion is estimated for Oct 2027, 70 months after the start.

Of 183 non-industry phase 2 interventional studies under Hodgkin Disease, half reached primary completion within 80 months of starting (the median), counting those still running; a quarter within 48 and three quarters within 115. This study's planned 70 months is below that.

Counting every sponsor, half of 206 studies reached it within 75 months; a quarter within 42 and three quarters within 111.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 10, 2020
First posted
Sep 23, 2020
StartActual
Nov 12, 2021
Primary completionEst.
Oct 2, 2027
CompletionEst.
Oct 2, 2027
Last update
Sep 22, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 22, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT04561206
Responsible party
Sponsor
First posted
Sep 23, 2020
Start date
Nov 12, 2021
Primary completion
Oct 2, 2027 (estimated)
Completion
Oct 2, 2027 (estimated)
Last update
Sep 22, 2026

Study contacts

Alex Herrera, MD
Contact
aherrera@coh.org
626-359-8111
Alex F Herrera
principal investigator · City of Hope Medical Center

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Brentuximab Vedotin · Nivolumab

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