Comparing standard therapy to immunotherapy for early stage Hodgkin lymphoma
Official title: 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
Run by National Cancer Institute (NCI) · NCT05675410 · Data updated 2026-11-12
This study is testing if adding immunotherapy to standard chemotherapy helps people with early stage Hodgkin lymphoma live longer and stay cancer-free.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Ages | 5 Years to 60 Years |
| Sex | All |
| Enrollment | 1875 (estimated) |
| Sponsor | National Cancer Institute (NCI) NIH |
| Drugs / interventions | brentuximab, nivolumab, chemotherapy, radiation, predniSONE, immunotherapy, Cyclophosphamide, doxorubicin |
| Locations | 419 sites (Birmingham, Alabama and 418 other locations) |
| Status | Recruiting |
| Started | May 11, 2023 |
| Main results expected | April 28, 2031 |
| Study ends | April 28, 2031 |
| Registry record updated | November 5, 2026 |
| Trial ID | NCT05675410 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are patients aged 5 to 60 with newly diagnosed, untreated classical Hodgkin lymphoma at stage I or II.
✕Probably not a fit
Patients with advanced stage Hodgkin lymphoma or those who have previously received treatment may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase III trial evaluates the effectiveness of adding immunotherapy, specifically brentuximab vedotin and nivolumab, to standard chemotherapy in patients with newly diagnosed early stage classical Hodgkin lymphoma. The study aims to compare progression-free survival between patients receiving standard treatment and those receiving the immunotherapy combination. It also assesses overall survival rates over a 12-year period for different response types to initial chemotherapy. The trial includes patients with measurable disease and utilizes PET scans to determine treatment response.
Why it matters
Potential benefit: If successful, this study could improve survival rates for patients with early stage Hodgkin lymphoma by enhancing the effectiveness of treatment.
How similar studies have gone: Other studies have shown promising results with immunotherapy approaches in similar patient populations, indicating potential for success in this trial.
Who can join: the full rules
Show full inclusion / exclusion 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
Where it's running
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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 -
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States Recruiting
Show 44 more locations
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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
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
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
+369 more sites. See ClinicalTrials.gov for the full list.
Study contacts
- Principal investigator: Kara M Kelly — Roswell Park Cancer Institute
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Combination treatment of brentuximab vedotin and nivolumab for relapsed Hodgkin lymphoma
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.