IRB Study Number 24-425
Status Recruiting
Institute Taussig Cancer Institute
Description
1.1 Primary Objective
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.
1.2 Secondary Objectives
1.2.1 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.
1.2.2 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.
1.2.3 To compare the rates of overall survival (OS) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL.
1.2.4 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 in patients with newly diagnosed PMBCL and evaluate the prognostic significance of such a finding.
Inclusion Criteria
3.2.1 Age
Age ≥ 2 years
3.2.2 Diagnosis
Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by WHO criteria
3.2.3 Performance Level
ECOG performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma
• COG Institutions: Use Karnofsky for patients ≥ 17 and < 18 years of age and Lansky for patients < 17 years of age. See “Performance Status Scales Scoring.”
3.2.4 Organ Function Requirements
3.2.4.1 Adequate renal function defined as:
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 to registration. Estimated creatinine clearance is based on actual body weight.
Estimated creatinine clearance = (140 – age) x wt (kg) x 0.85 (if female)
72 x creatinine (mg/dl)
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 creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73 m2, or
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/gender as follows: (See protocol)
3.2.4.2 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. Please refer to 3.2.12 for exclusion criteria and Section 5.0 for dose modifications in patients with hepatic impairment.
3.2.4.3 Adequate cardiac function defined as:
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.
3.2.4.4 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
3.2.4.5 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
3.2.4.6 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
3.2.5 Prior Therapy
Administration of prior anti-cancer therapy except as outlined below:
a. A short course (≤ 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms.
b. A single course of COP (cyclophosphamide, vincristine, and prednisone)
c. One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric mature B-NHL induction therapy (such as ANHL1131), or intrathecal chemotherapy that has not started more than 21 days prior to enrollment.
3.2.6 Active ischemic heart disease or heart failure.
3.2.7 Active uncontrolled infection
3.2.8 CNS involvement of lymphoma.
3.2.9 Previous cancer that required systemic chemotherapy and/or thoracic radiation. Other cancers will be permitted if in remission x 3 years.
3.2.10 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.
3.2.11 In patients < 18 years of age Hepatitis B serologies consistent with past or current infections
3.2.12 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.
3.2.13 Pregnancy and Breastfeeding
3.2.13.1 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.
3.2.13.2 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.
3.2.13.3 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.
3.2.14 Regulatory Requirements
3.2.14.1 All patients and/or their parents or legal guardians must sign a written informed consent.
3.2.14.2 All institutional, FDA, and NCI requirements for human studies must be met.
