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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