A Randomized Phase 3 Trial of Nivolumab in Combination with Chemo-immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma.
1. To determine if nivolumab + chemo-immunotherapy results in a superior long term PFS (events defined as disease progression confirmed by central review or death) when compared with chemo- immunotherapy alone in patients with newly diagnosed primary mediastinal B-cell lymphoma.
2. To compare the rates of efficacy-related EFS (eEFS) (events defined as progression, change in therapy due to finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, or death) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL.
3. To compare the rates of therapy-related EFS (tEFS) (events defined as relapse/progression, change in therapy for any reason, biopsy + disease after 6 cycles of therapy, secondary malignancy (SMN) or death) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL.
4. To compare the rates of overall survival (OS) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL.
5. To establish the rate of a positive PET-CT (defined as Deauville score 4 or 5) at the completion of 6 cycles of nivolumab + R-CHOP/DA-EPOCH-R and R-CHOP/DA-EPOCH-R.
Any Site
- Rutgers Cancer Institute of New Jersey
- Robert Wood Johnson Medical School
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
- Previous cancer that required systemic chemotherapy and/or thoracic radiation. Other
cancers will be permitted if in remission x 3 years
- 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
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.