Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma

J
Jenny Belsky, DO

Primary Investigator

Enrolling By Invitation
2 years and older
All
Phase 3
192 participants needed
1 Location

Brief description of study

What is the purpose of this study?
This phase III trial compares the effects of nivolumab with chemo-immunotherapy versushemo-immunotherapy alone in treating patients with newly diagnosed primary mediastinal B-cell lymphoma (PMBCL). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancergrow and spread. Treatment for PMBCL involves chemotherapy combined with anunotherapy called rituximab. Chemotherapy drugs work in different ways to stop the growthher by killing the cells, by stopping them from dividing, or by stoppinghem from spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. Thisy help the immune system kill cancer cells. Giving nivolumab with chemo-immunotherapy may help treat patients with PMBCL.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the study?
  • Patients are randomly assigned to backbone therapy or backbone therapy + nivolumab within each of 6 strata. The strata are determined by physician's choice of backbone (DA-EPOCH-R vs. R-CHOP vs. R-CHOP + RT) and whether or not the patient had 1 prior cycle ofherapy.
  • ARM A (DA-EPOCH-R): Patients receive prednisone or prednisolone orally (PO) once daily (QD)days 1-5 and rituximab intravenously (IV) or rituximab and hyaluronidase humanubcutaneously (SC) over 5 minutes on day 1 or 5. Patients also receive etoposide phosphate, doxorubicin hydrochloride, and vincristine sulfate IV over 96 hours on days 1-4 andyclophosphamide IV over 30-60 minutes on day 5. Beginning 24-72 hours after completingyclophosphamide, patients receive filgrastim or pegylated filgrastim SC daily until absoluteutrophil count (ANC) is >= 500/uL after the expected nadir. Treatment repeats every 21 daysup to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-positron emissiongraphy and computed tomography scan (FDG-PET/CT) on study,
  • ARM B (DA-EPOCH-R + NIVOLUMAB): Patients receive treatment as in Arm A. Patients also receivevolumab IV over 30 minutes on day 1. Patients also undergo FDG-PET/CT on study,
  • ARM C (R-CHOP): Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximabV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5. Patients alsove cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 1-15utes or up to 60 minutes, and vincristine sulfate IV over 1 or up to 60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of) in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/CT on study,
  • ARM D (R-CHOP + NIVOLUMAB): Patients receive treatment as in Arm C. Patients also receivevolumab IV over 30 minutes on day 1. Patients also undergo FDG-PET/CT on study,
  • ARM E (R-CHOP + RADIOTHERAPY): Patients receive treatment as in Arm C. Within 6-8 weeks afterhemotherapy, patients undergo radiation therapy over 25 fractions. Patientsundergo FDG-PET/CT on study,
  • ARM F (R-CHOP + RADIOTHERAPY + NIVOLUMAB): Patients receive treatment as in Arm D. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients also undergo FDG-PET/CT on study,
  • After completion of study treatment, patients are followed up every 3 months for year 1,very 6 months for years 2-3, and annually thereafter.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Primary Mediastinal (Thymic) Large B-Cell Lymphoma, Riley
  • Age: 2 Years
  • Gender: All

Inclusion Criteria:
  • Age >= 2 years
  • Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL)defined by World Health Organization (WHO) criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOGus of 3 if poor performance is related to lymphoma
    • Children's Oncology Group (COG) Institutions: Use Karnofsky for patients >= 17d < 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 havebeen obtained within 28 days prior to registration. Estimated creatinine clearance isbased on actual body weight
  • Pediatric Patients (age < 18 years): The following must have been obtained within 14days prior to registration:
    • Measured or calculated (based on institutional standard) creatinine clearance ordioisotope 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 serumbased 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>= 50% by radionuclide angiogram
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviralherapy 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 virald must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treatedd cured. For patients with HCV infection who are currently on treatment, they aregible if they have an undetectable HCV viral load
  • All patients and/or their parents or legal guardians must sign a written informed
  • 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-relatedymptoms
    • A single course of COP (cyclophosphamide, vincristine, and prednisone)
    • One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric matureB-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131), orhecal chemotherapy that has not started more than 21 days prior to
  • 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. Otherwill be permitted if in remission x 3 years
  • Active autoimmune disease that has required systemic treatment (such as diseasedifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years.Replacement therapy such as thyroxine, insulin or physiologic corticosteroid fordrenal 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
  • 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 havebeen noted for several of the study drugs. A pregnancy test is required for femalehildbearing potential
  • Sexually active patients of reproductive potential who have not agreed to use a highlyve contraceptive method (failure rate of < 1% per year when used consistentlyd correctly) for the duration of their study participation
  • Lactating females are not eligible unless they have agreed not to breastfeed theirg with the first dose of study therapy and for at least 6 months afterhe last dose of rituximab

Updated on 23 Sep 2024. Study ID: NCI-2021-01071, PHO-COG-ANHL1931, 13206
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