Nivolumab With Chemo-Immunotherapy for the Treatment of Primary Mediastinal B-Cell Lymphoma

What is the Purpose of this Study?

This study focuses on individuals who have been diagnosed with primary mediastinal B Cell lymphoma (PMBCL). PMBCL is a type of cancer that occurs in the upper chest (in an area called the mediastinum). The study will evaluate how well the addition of an experimental drug called nivolumab to chemo-immunotherapy works when given to children, adolescents, and adults with PMBCL. Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab. This combination is also known as chemo-immunotherapy. There are 2 types of chemo-immunotherapy regimens for PMBCL: R-CHOP and DA-EPOCH-R. Nivolumab is a type of cancer treatment that uses the immune system to fight cancer. The study will use nivolumab with chemo-immunotherapy and compare the results with only chemo-immunotherapy in newly diagnosed PMBCL. In so doing, researchers hope to identify the best way to treat PMBCL while also improving outcomes. Participants will be randomly assigned to 1 of 3 treatment groups. Treatment 1 is the chemo-immunotherapy regimen DA-EPOCH-R with or without nivolumab. Treatment 2 is the chemo-immunotherapy regimen R-CHOP, with or without nivolumab. Treatment 3 is the chemo-immunotherapy regimen R-CHOP in combination with radiation treatments, with or without nivolumab.

Eligibility

* Age \>= 2 years
* Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma

Inclusion Criteria:

* Age \>= 2 years
* Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma
* Children's Oncology Group (COG) Institutions: Use Karnofsky for patients \>= 17 and \< 18 years of age and Lansky for patients \< 17 years of age
* Adults (age 18 or older): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula. 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
* Pediatric Patients (age \< 18 years): The following must have been obtained within 14 days prior to registration:
* Measured or calculated (based on institutional standard) creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2, or
* Serum creatinine =\< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/gender as follows:
* Age : 2 to \< 6 year; Maximum serum creatinine (mg/dL): 0.8 (male; 0.8 (female)
* Age : 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female)
* Age : 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
* Age : 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
* Age : \>= 16 years to \< 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
* Patients with abnormal liver function will be eligible to enroll if the lab abnormality is thought to be due to the lymphoma or Gilbert's syndrome
* Age \>= 18 years: Ejection fraction of \>= 50% by echocardiogram
* Age \< 18 years: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram
* 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
* 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

Exclusion Criteria:

* Administration of prior anti-cancer therapy except as outlined below:
* A short course (=\< 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms
* A single course of COP (cyclophosphamide, vincristine, and prednisone)
* One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131), or intrathecal chemotherapy that has not started more than 21 days prior to enrollment
* Active ischemic heart disease or heart failure
* Active uncontrolled infection
* Central nervous system (CNS) involvement of lymphoma
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this trial
* Active autoimmune disease that has required systemic treatment (such as disease modifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years. Replacement therapy such as thyroxine, insulin or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment
* In patients \< 18 years of age hepatitis B serologies consistent with past or current infections
* Patients with severe hepatic impairment (Child-Pugh class C or serum total bilirubin \> 5.0 mg/dL) unless thought to be due to lymphoma or Gilbert's syndrome
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of \< 1% per year when used consistently and correctly) for the duration of their study participation
* Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last dose of rituximab

Show less

Where can I participate?

CS Cancer at Cedars-Sinai Medical Center

More about this Clinical Trial

What is the full name of this clinical trial?

ANHL1931: A Randomized Phase 3 Trial of Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma ^

Study Details

Disease Type/Condition

Non-Hodgkin's Lymphoma

Principal Investigator

Baca, Nicole

Co-Investigators

Akil Merchant, Edwin Posadas, Fataneh Majlessipour, Joshua Sasine, Justin Darrah, Leo Mascarenhas, Noah Merin, Ronald Paquette

Age Group

Both

Phase

III

IRB Number

STUDY00003456

ClinicalTrials.gov ID

NCT04759586

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org