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NCT05675410From ClinicalTrials.govRecruiting

A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab

A Randomized Phase 3 Interim Response Adapted Trial Comparing Standard Therapy With Immuno-oncology Therapy for Children and Adults With Newly Diagnosed Stage I and II Classic Hodgkin Lymphoma

  • Lugano Classification Limited Stage Hodgkin Lymphoma AJCC v8

At a glance

Phase
Phase 3
Study type
Interventional
Sponsor
National Cancer Institute (NCI)
Enrolment target
1,875
Started
11 May 2023
Main results due
28 April 2031
Study sites
415
Registry updated
29 September 2026

Can you take part?

  • Ages 5 years to 60 years.
  • Open to any sex.
  • You need the condition being studied — healthy volunteers are not accepted.

These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.

Read the full eligibility criteria
Inclusion Criteria:

* Patients must be 5 to 60 years of age at the time of enrollment
* Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified \[NOS\]) with stage I or II disease
* Patients must have bidimensionally measurable disease (at least one lesion with longest diameter \>= 1.5 cm)
* Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained
* Pediatric patients (age 5-17 years) with known or suspected mediastinal disease must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease.

  * Note: Pediatric patients who have received both a CT chest and upright PA CXR may meet the definition of bulk through either modality.
* Patients \>= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2
* Patients =\< 17 years of age must have a Lansky performance score of \>= 50
* Pediatric patients (age 5-17 years): A serum creatinine based on age/sex as follows (within 28 days prior to enrollment):

  * 2 to \< 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female)
  * 6 to \< 10 years (age): 1 mg/dL (male), 1 mg/dL (female)
  * 10 to \< 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female)
  * 13 to \< 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female)
  * \>= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment) OR a glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
  * Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* For adult patients (age 18 years or older) (within 28 days prior to enrollment): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
* Total bilirubin =\< 2 x upper limit of normal (ULN) (within 28 days prior to enrollment)

  * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
* Aspartate aminotransferase (AST) =\< 3 x ULN (within 28 days prior to enrollment)

  * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
* Alanine aminotransferase (ALT) =\< 3 x ULN (within 28 days prior to enrollment)

  * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
* Shortening fraction of \>= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 28 days prior to enrollment) or ejection fraction of \>= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 28 days prior to enrollment)
* Diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 28 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of \> 92% on room air
* Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

Exclusion Criteria:

* Patients with nodular lymphocyte predominant Hodgkin lymphoma
* Patients with a history of active interstitial pneumonitis or interstitial lung disease
* Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients
* Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills
* Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to \> 10 mg daily predniSONE for patients \>= 18 years or \> 0.5 mg/kg \[up to 10 mg/day\] for patients \< 18 years) or other immunosuppressive medications within 14 days prior to enrollment

  * Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=\< 10 mg daily for patients \>= 18 years or =\< 0.5 mg/kg \[up to 10 mg/day\] predniSONE equivalents) are permitted in the absence of active autoimmune disease
  * Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1
  * Short term use of corticosteroids for premedication or treatment of an allergy or hypersensitivity is considered an acceptable use of corticosteroids.
* Patients with peripheral neuropathy \> grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL
* Prior solid organ transplant
* Prior allogeneic stem cell transplantation
* Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, bacillus Calmette Guerin \[BCG\], oral polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment
* Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer

  * Men and women of childbearing potential (WOCBP) must use effective contraception during the study and for 2 months for WOCBP and 4 months for men, after last dose of brentuximab vedotin
  * WOCBP must continue contraception for a period of at least 5 months after the last dose of nivolumab
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

What this study is about

In the sponsor’s own words, from the registry.

This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.

Study sites(415)

  • Children's Hospital of Alabama

    Birmingham, Alabama, United States

    Recruiting

  • USA Health Strada Patient Care Center

    Mobile, Alabama, United States

    Recruiting

  • Providence Alaska Medical Center

    Anchorage, Alaska, United States

    Recruiting

  • CTCA at Western Regional Medical Center

    Goodyear, Arizona, United States

    Recruiting

  • Banner Children's at Desert

    Mesa, Arizona, United States

    Recruiting

  • Phoenix Childrens Hospital

    Phoenix, Arizona, United States

    Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, United States

    Recruiting

  • Mercy Cancer Center - Carmichael

    Carmichael, California, United States

    Recruiting

  • Mercy San Juan Medical Center

    Carmichael, California, United States

    Recruiting

  • City of Hope Corona

    Corona, California, United States

    Recruiting

  • UC Irvine Health Cancer Center-Newport

    Costa Mesa, California, United States

    Recruiting

  • Kaiser Permanente Downey Medical Center

    Downey, California, United States

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, United States

    Recruiting

  • Kaiser Permanente Dublin

    Dublin, California, United States

    Recruiting

  • Mercy Cancer Center - Elk Grove

    Elk Grove, California, United States

    Recruiting

  • Kaiser Permanente-Fremont

    Fremont, California, United States

    Recruiting

  • Kaiser Permanente Fresno Orchard Plaza

    Fresno, California, United States

    Suspended

  • Kaiser Permanente-Fresno

    Fresno, California, United States

    Recruiting

  • City of Hope Seacliff

    Huntington Beach, California, United States

    Recruiting

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, United States

    Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California, United States

    Recruiting

  • City of Hope Antelope Valley

    Lancaster, California, United States

    Recruiting

  • Loma Linda University Medical Center

    Loma Linda, California, United States

    Recruiting

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, United States

    Recruiting

  • City of Hope at Long Beach Elm

    Long Beach, California, United States

    Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California, United States

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, United States

    Recruiting

  • Valley Children's Hospital

    Madera, California, United States

    Recruiting

  • Kaiser Permanente- Modesto MOB II

    Modesto, California, United States

    Suspended

  • Kaiser Permanente-Modesto

    Modesto, California, United States

    Recruiting

  • City of Hope Newport Beach

    Newport Beach, California, United States

    Recruiting

  • Kaiser Permanente-Oakland

    Oakland, California, United States

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, United States

    Recruiting

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, United States

    Recruiting

  • Mercy Cancer Center - Rocklin

    Rocklin, California, United States

    Recruiting

  • Kaiser Permanente Downtown Commons

    Sacramento, California, United States

    Recruiting

  • Mercy Cancer Center - Sacramento

    Sacramento, California, United States

    Recruiting

  • Sutter Medical Center Sacramento

    Sacramento, California, United States

    Recruiting

  • Kaiser Permanente-South Sacramento

    Sacramento, California, United States

    Recruiting

  • Rady Children's Hospital - San Diego

    San Diego, California, United States

    Recruiting

  • Naval Medical Center -San Diego

    San Diego, California, United States

    Recruiting

  • Kaiser Permanente-San Francisco

    San Francisco, California, United States

    Recruiting

  • Kaiser Permanente-Santa Teresa-San Jose

    San Jose, California, United States

    Recruiting

  • Kaiser Permanente San Leandro

    San Leandro, California, United States

    Recruiting

  • Kaiser San Rafael-Gallinas

    San Rafael, California, United States

    Recruiting

  • Santa Barbara Cottage Hospital

    Santa Barbara, California, United States

    Recruiting

  • Kaiser Permanente-Santa Rosa

    Santa Rosa, California, United States

    Recruiting

  • City of Hope South Pasadena

    South Pasadena, California, United States

    Recruiting

  • Kaiser Permanente-South San Francisco

    South San Francisco, California, United States

    Recruiting

  • City of Hope South Bay

    Torrance, California, United States

    Recruiting

  • City of Hope Upland

    Upland, California, United States

    Recruiting

  • Kaiser Permanente-Vallejo

    Vallejo, California, United States

    Recruiting

  • Kaiser Permanente-Walnut Creek

    Walnut Creek, California, United States

    Recruiting

  • Woodland Memorial Hospital

    Woodland, California, United States

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, United States

    Recruiting

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, United States

    Recruiting

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, United States

    Recruiting

  • Memorial Hospital North

    Colorado Springs, Colorado, United States

    Recruiting

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, United States

    Recruiting

  • Poudre Valley Hospital

    Fort Collins, Colorado, United States

    Recruiting

Showing 60 of 415 sites — filter to narrow it down. 398 of the 415 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.

Source: ClinicalTrials.gov record NCT05675410. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.

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A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and | Trialion