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Classic Hodgkin LymphomaPhase 2NCT03057795

Nivolumab & Brentuximab Vedotin Consolidation After Autologous SCT in Patients With High-Risk Classical Hodgkin Lymphoma

A Phase 2 study testing Brentuximab Vedotin, Laboratory Biomarker Analysis and Nivolumab in people with Classic Hodgkin Lymphoma and Recurrent Hodgkin Lymphoma, run by City of Hope Medical Center at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial studies how well nivolumab and brentuximab vedotin work after stem cell transplant in treating patients with high-risk classical Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Brentuximab Vedotin, Laboratory Biomarker Analysis and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
6 sitesUnited States
Study dates
3 May 2017to 25 Feb 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent
  • Agreement to allow the use of archival tissue from pre-ASCT tumor biopsies
  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 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
  • Have high-risk relapsed or refractory Hodgkin lymphoma (HL), defined as at least one of the following:
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  • Primary refractory disease to front-line therapy
  • Relapse within 1 year of completing front-line therapy
  • Extranodal involvement at the time of pre-ASCT relapse
  • B symptoms at pre-ASCT relapse
  • More than one type of pre-ASCT salvage therapy required
  • Planning to receive or have received autologous stem cell transplantation (ACST) per institutional standards as part of standard of care
  • Pre-ASCT participants may consent but will not be eligible to begin treatment until after ASCT, and will have to fulfill all inclusion and exclusion criteria before starting protocol
  • All participants must initiate day 1 of protocol therapy within 30-60 days post stem cell reinfusion; study PI can grant exception for a patient to start as late as 75 days post stem cell reinfusion with a reasonable justification for a delay (e.g. recovery from post -ASCT toxicity) and this will not be a protocol deviation, nor require an exception to be filled
  • Recovery from ASCT toxicity as defined as outpatient status, able to drink, eat normally, and do not need intravenous hydration prior to day 1 of therapy
  • Achieved at least stable disease to salvage treatment determined by positron emission tomography (PET)/computed tomography (CT) using 2014 Lugano Classification prior to ASCT
  • Brentuximab vedotin naive OR had at least stable disease by Lugano Classification to prior brentuximab vedotin treatment
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelets >= 50,000/mm^3
  • Hemoglobin >= 8 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or 3 x ULN for Gilbert's disease
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine clearance >= 40 mL/min per 24 hour urine collection or the Cockcroft-Gault formula
  • Calculated per institutional standard
  • Forced expiratory volume in one second (FEV1) and carbon monoxide diffusion capacity (DLCO) (adjusted for hemoglobin [Hb]) >= 50% adjusted
  • Women of childbearing potential (WOCBP) only: Negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG])
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Woman of childbearing potential (WOCBP): use two effective methods of contraception (hormonal or barrier method) or be surgically sterile, or abstain from heterosexual activity for the course of the study through 7 months post last dose of nivolumab
  • WOCBP defined as not being surgically sterilized or have not been free from menses for > 1 year
  • Male: use two effective methods of contraception (barrier method) or abstain from heterosexual activity with the first dose of study therapy through 7 months post last dose of nivolumab

Who cannot join

  • Post-ASCT anti-lymphoma or investigational therapy; immediate post-ASCT consolidative radiation therapy is allowed as long as it occurs prior to initiation of study therapy; baseline imaging and pulmonary function tests (PFTs) must be performed after completion of radiation
  • Previous allogeneic transplant
  • Total carmustine (BCNU) dose of > 600 mg/m^2 with prior treatments including transplant conditioning regimen
  • 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)
  • Refractory to prior brentuximab vedotin (i.e. progression while on treatment)
  • Refractory to prior anti-PD-1/PD-L1 agent
Show all 36Show fewer
  • History of prior >= grade 3 hypersensitivity to either brentuximab vedotin or nivolumab
  • History of another primary malignancy that has not been in remission for at least 3 years; exceptions include:
  • Basal cell carcinoma of the skin or
  • Squamous cell carcinoma of the skin that has undergone potentially curative therapy or
  • In situ cervical cancer
  • Known active central nervous system (CNS) involvement by lymphoma, including parenchymal and/or lymphomatous meningitis
  • History of progressive multifocal leukoencephalopathy (PML)
  • Grade >= 2 peripheral neuropathy at the present time
  • Prior diagnosis of inherited or acquired immunodeficiency
  • 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
  • Uncontrolled illness including ongoing or active infection
  • History of or active pneumonitis or interstitial lung disease:
  • For history of pneumonitis to be an exclusion, patient had to have required supplemental oxygen or corticosteroid treatment; radiographic changes alone are not an exclusion
  • An active, known or suspected autoimmune disease; the following are exceptions:
  • Vitiligo
  • Hemolytic anemia associated with the lymphoma (history of or at the present time)
  • 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
  • Active or known history (standard pre-ASCT assessments) of:
  • Hepatitis B or C infection
  • Human immunodeficiency virus (HIV)
  • Acquired immunodeficiency syndrome (AIDS)
  • Women who are pregnant or lactating
  • 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
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • 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)

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • City of Hope Medical Center

    Duarte, California, 91010

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase 2 Study of Nivolumab and Brentuximab Vedotin Consolidation After Autologous Stem Cell Transplantation in Patients With High-Risk Classical Hodgkin Lymphoma

This phase II trial studies how well nivolumab and brentuximab vedotin work after stem cell transplant in treating patients with high-risk classical Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and brentuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Assess the efficacy of nivolumab plus brentuximab vedotin consolidation after autologous stem cell transplantation (ASCT) in participants with relapsed/refractory Hodgkin lymphoma (HL), as assessed by 18-month progression-free survival (PFS).

SECONDARY OBJECTIVES:

  1. Estimate the overall survival (OS), the cumulative incidence of relapse/progression, the cumulative incidence of non-relapse mortality (TRM) in participants with relapsed/ refractory HL who receive nivolumab plus brentuximab vedotin consolidation after ASCT.

II. Estimate the overall response rate to nivolumab plus brentuximab vedotin therapy in participants with measurable disease after ASCT.

III. Establish the safety and tolerability of nivolumab plus brentuximab vedotin when used as consolidation after ASCT in participants with relapsed/ refractory HL.

EXPLORATORY OBJECTIVES:

  1. Evaluate the Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC) definition of indeterminate response to guide the management of patients regarding treatment past progressive disease.

II. Explore the impact of nivolumab plus brentuximab vedotin therapy on immune reconstitution after ASCT.

III. Explore the prognostic impact of and temporal dynamics of minimal residual disease (MRD) in the peripheral blood as assessed by the next-generation sequencing-based ClonoSEQ platform.

IV. Explore the prognostic impact of 9p24.1 abnormalities in tumor tissue assessed by fluorescence in situ hybridization (FISH) on outcomes after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy.

  1. Explore the relationship between immune cells and Hodgkin and Reed/Sternberg (HRS) in tumor samples by 6-color quantitative spatial image analysis using the Vectra system, and correlate with outcome after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy.

VI. Explore whether genetic alterations (e.g. gene expression profiles or genetic mutations) in HL tumor samples are associated with outcome after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy.

OUTLINE:

Beginning 30-60 days post-ASCT, 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 8 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 100 days, at 3, 6, 12, and 18 months from start of treatment, and then biannually thereafter.

Being tested
Brentuximab Vedotin, Laboratory Biomarker Analysis, Nivolumab
Medical subject headings
Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brentuximab VedotinDrug

    Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT03057795
Study groupRoleWhat they receive
Treatment (brentuximab vedotin, nivolumab)ExperimentalBeginning 30-60 days post-ASCT, patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Brentuximab Vedotin; Other: Laboratory Biomarker Analysis; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival at 18 Months

    Progression-free survival will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error. When there is no censoring in progression-free survival prior to 18 months after the first dose of study treatment, the observed 18-month progression-free survival will be compared to the baseline of 65% by one-sided exact test of binomial proportion. In case of censoring in progression-free survival prior to 18 months after the first dose of study treatment, the Kaplan-Meier estimate for 18-month progression-free survival along with the Greenwood standard error estimator will be used for the testing of null hypothesis at 65%. Hodgkin Lymphoma(HL) response/progression was evaluated using 2014 Lugano Classification [Cheson, Journal of Clinical Oncology 2014 Sep 20;32(27):3059-68].

    Measured: From the first dose of study treatment to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed at 18 months.

Secondary outcomes (1)

  1. Overall Survival at 18 Months

    Overall survival will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.

    Measured: From the first dose of study treatment to death from any cause, assessed up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2017
  2. Study start3 May 2017
  3. Primary completion30 Jan 2021
  4. Study completion25 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03057795
Sponsor's protocol ID
16378
Other IDs
NCI-2017-00222, 16378, P30CA033572
Status last verified
Oct 2026
First submitted
14 Feb 2017
Last updated
26 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Herrera AF, Chen L, Nieto Y, Holmberg L, Johnston P, Mei M, Popplewell L, Armenian S, Cao T, Farol L, Sahebi F, Spielberger R, Chen R, Nademanee A, Puverel S, Nwangwu M, Lee P, Song J, Skarbnik A, Kennedy N, Peters L, Rosen ST, Kwak LW, Forman SJ, Feldman T. Brentuximab vedotin plus nivolumab after autologous haematopoietic stem-cell transplantation for adult patients with high-risk classic Hodgkin lymphoma: a multicentre, phase 2 trial. Lancet Haematol. 2023 Jan;10(1):e14-e23. doi: 10.1016/S2352-3026(22)00318-0. Epub 2022 Nov 17.

    PubMed 36403579

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brentuximab Vedotin, Laboratory Biomarker Analysis and Nivolumab in people with Classic Hodgkin Lymphoma and Recurrent Hodgkin Lymphoma, run by City of Hope Medical Center at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival at 18 Months (time frame: From the first dose of study treatment to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed at 18 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03057795, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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