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NCT04759586 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-08-24

This phase III trial compares the effects of nivolumab with chemo-immunotherapy versus chemo-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 cancer cells to grow and spread. Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them 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. This may help the immune system kill cancer cells. Giving nivolumab with chemo-immunotherapy may help treat patients with PMBCL.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
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/sex 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
healthy Volunteers
false
minimum Age
2 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    See Detailed Description
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Bone Marrow Aspiration
    3. Procedure: Bone Marrow Biopsy
    4. Procedure: Computed Tomography
    5. Drug: Cyclophosphamide
    6. Drug: Doxorubicin Hydrochloride
    7. Procedure: Echocardiography Test
    8. Drug: Etoposide Phosphate
    9. Biological: Filgrastim
    10. Procedure: Lumbar Puncture
    11. Biological: Pegfilgrastim
    12. Procedure: Positron Emission Tomography
    label
    Arm A (DA-EPOCH-R)
    type
    ACTIVE_COMPARATOR
  2. description
    Patients receive treatment as in Arm A. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and LP for CSF collection during screening. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Bone Marrow Aspiration
    3. Procedure: Bone Marrow Biopsy
    4. Procedure: Computed Tomography
    5. Drug: Cyclophosphamide
    6. Drug: Doxorubicin Hydrochloride
    7. Procedure: Echocardiography Test
    8. Drug: Etoposide Phosphate
    9. Biological: Filgrastim
    10. Procedure: Lumbar Puncture
    11. Biological: Nivolumab
    12. Biological: Pegfilgrastim
    label
    Arm B (DA-EPOCH-R, nivolumab)
    type
    EXPERIMENTAL
  3. description
    Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5. Patients also receive cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 1-15 minutes 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 treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Bone Marrow Aspiration
    3. Procedure: Bone Marrow Biopsy
    4. Procedure: Computed Tomography
    5. Drug: Cyclophosphamide
    6. Drug: Doxorubicin Hydrochloride
    7. Procedure: Echocardiography Test
    8. Procedure: Lumbar Puncture
    9. Procedure: Positron Emission Tomography
    10. Drug: Prednisolone
    11. Drug: Prednisone
    12. Biological: Rituximab
    label
    Arm C (R-CHOP)
    type
    ACTIVE_COMPARATOR
  4. description
    Patients receive treatment as in Arm C. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Bone Marrow Aspiration
    3. Procedure: Bone Marrow Biopsy
    4. Procedure: Computed Tomography
    5. Drug: Cyclophosphamide
    6. Drug: Doxorubicin Hydrochloride
    7. Procedure: Echocardiography Test
    8. Procedure: Lumbar Puncture
    9. Biological: Nivolumab
    10. Procedure: Positron Emission Tomography
    11. Drug: Prednisolone
    12. Drug: Prednisone
    label
    Arm D (R-CHOP, nivolumab)
    type
    EXPERIMENTAL
  5. description
    Patients receive treatment as in Arm C. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Bone Marrow Aspiration
    3. Procedure: Bone Marrow Biopsy
    4. Procedure: Computed Tomography
    5. Drug: Cyclophosphamide
    6. Drug: Doxorubicin Hydrochloride
    7. Procedure: Echocardiography Test
    8. Procedure: Lumbar Puncture
    9. Procedure: Positron Emission Tomography
    10. Drug: Prednisolone
    11. Drug: Prednisone
    12. Radiation: Radiation Therapy
    label
    Arm E (R-CHOP, radiation therapy)
    type
    ACTIVE_COMPARATOR
  6. description
    Patients receive treatment as in Arm D. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Bone Marrow Aspiration
    3. Procedure: Bone Marrow Biopsy
    4. Procedure: Computed Tomography
    5. Drug: Cyclophosphamide
    6. Drug: Doxorubicin Hydrochloride
    7. Procedure: Echocardiography Test
    8. Procedure: Lumbar Puncture
    9. Biological: Nivolumab
    10. Procedure: Positron Emission Tomography
    11. Drug: Prednisolone
    12. Drug: Prednisone
    label
    Arm F (R-CHOP, nivolumab, radiation therapy)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Undergo blood and CSF sample collection
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Sample Collection
    4. Specimen Collection
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Undergo bone marrow biopsy and aspiration
    name
    Bone Marrow Aspiration
    type
    PROCEDURE
  3. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Undergo bone marrow biopsy and aspiration
    name
    Bone Marrow Biopsy
    other Names
    1. Biopsy of Bone Marrow
    2. Biopsy, Bone Marrow
    type
    PROCEDURE
  4. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Undergo CT or PET/CT
    name
    Computed Tomography
    other Names
    1. CAT
    2. CAT Scan
    3. Computed Axial Tomography
    4. Computerized Axial Tomography
    5. Computerized axial tomography (procedure)
    6. Computerized Tomography
    7. Computerized Tomography (CT) scan
    8. CT
    9. CT Scan
    10. Diagnostic CAT Scan
    11. Diagnostic CAT Scan Service Type
    12. tomography
    type
    PROCEDURE
  5. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Asta B 518
    4. B 518
    5. B-518
    6. B518
    7. Carloxan
    8. Ciclofosfamida
    9. Ciclofosfamide
    10. Cicloxal
    11. Clafen
    12. Claphene
    type
    DRUG
  6. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Given IV
    name
    Doxorubicin Hydrochloride
    other Names
    1. 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    2. ADM
    3. Adriacin
    4. Adriamycin
    5. Adriamycin Hydrochloride
    6. Adriamycin PFS
    7. Adriamycin RDF
    8. ADRIAMYCIN, HYDROCHLORIDE
    9. Adriamycine
    10. Adriblastina
    11. Adriblastine
    12. Adrimedac
    type
    DRUG
  7. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Undergo ECHO
    name
    Echocardiography Test
    other Names
    1. EC
    2. Echocardiography
    type
    PROCEDURE
  8. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    description
    Given IV
    name
    Etoposide Phosphate
    other Names
    1. Etopophos
    type
    DRUG
  9. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    description
    Given SC
    name
    Filgrastim
    other Names
    1. Filgrastim Biosimilar Filgrastim-sndz
    2. Filgrastim Biosimilar Tbo-filgrastim
    3. Filgrastim XM02
    4. Filgrastim-aafi
    5. Filgrastim-ayow
    6. Filgrastim-sndz
    7. G-CSF
    8. Granix
    9. Neupogen
    10. Neutroval
    11. Nivestim
    12. Nivestym
    type
    BIOLOGICAL
  10. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    3. Arm C (R-CHOP)
    4. Arm D (R-CHOP, nivolumab)
    5. Arm E (R-CHOP, radiation therapy)
    6. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Undergo LP
    name
    Lumbar Puncture
    other Names
    1. LP
    2. Spinal Tap
    type
    PROCEDURE
  11. arm Group Labels
    1. Arm B (DA-EPOCH-R, nivolumab)
    2. Arm D (R-CHOP, nivolumab)
    3. Arm F (R-CHOP, nivolumab, radiation therapy)
    description
    Given IV
    name
    Nivolumab
    other Names
    1. ABP 206
    2. BCD-263
    3. BMS 936558
    4. BMS-936558
    5. BMS936558
    6. CMAB819
    7. MDX 1106
    8. MDX-1106
    9. MDX1106
    10. NIVO
    11. Nivolumab Biosimilar ABP 206
    12. Nivolumab Biosimilar BCD-263
    type
    BIOLOGICAL
  12. arm Group Labels
    1. Arm A (DA-EPOCH-R)
    2. Arm B (DA-EPOCH-R, nivolumab)
    description
    Given SC
    name
    Pegfilgrastim
    other Names
    1. Cegfila
    2. Dulastin
    3. Dyrupeg
    4. Filgrastim SD-01
    5. filgrastim-SD/01
    6. Fulphila
    7. Fylnetra
    8. G-Lasta
    9. Grasustek
    10. HSP-130
    11. Jinyouli
    12. Neulasta
    type
    BIOLOGICAL
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
244
type
ESTIMATED
Registered outcome plans (not posted results)
other Outcomes
  1. description
    Analysis will be by paired t-test (for pre- vs. post-treatment measurements) or two-sample equal-variance t-test (for comparisons of nivolumab vs. non-nivolumab or responders \[complete response/partial response\] vs. non-responders \[stable disease/progressive disease\]).
    measure
    Immune profile of patients treated with nivolumab + chemo-immunotherapy
    time Frame
    Up to 7 years
  2. description
    Will be described using point estimates and Clopper-Pearson 95% confidence intervals for the complete response rate overall and in each treatment arm separately.
    measure
    Complete response rate
    time Frame
    At the completion of initial planned therapy
primary Outcomes
  1. description
    The primary analysis will be a one-sided Log-rank test stratified by choice of backbone and radiation therapy and whether the patient had a cycle of therapy prior to enrolling.
    measure
    Progression-free survival (PFS)
    time Frame
    From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 7 years
secondary Outcomes
  1. description
    Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as progression, change in therapy due to a finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, and death.
    measure
    Efficacy-related event-free survival
    time Frame
    Up to 7 years
  2. description
    Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as progression, change in therapy due to a finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, and death.
    measure
    Therapy-related event-free survival
    time Frame
    Up to 7 years
  3. description
    Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as only death.
    measure
    Overall survival
    time Frame
    Up to 7 years
  4. description
    Will be analyzed descriptively with a point estimate and Clopper-Pearson 95% confidence interval in the trial overall and in each treatment arm separately. The prognostic significance of positive PET after 6 cycles of therapy will be evaluated using a Cox proportional hazards regression on PFS with PET result (positive versus \[vs.\] negative), choice of backbone (rituximab \[R\]-cyclophosphamide, doxorubicin, vincristine, and prednisone \[CHOP\] + radiation therapy \[RT\] regardless of end-of-therapy imaging vs. R-CHOP without RT unless biopsy positive at end-of-therapy vs. dose-adjusted \[DA\]-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin \[EPOCH\]-R without RT unless biopsy positive at end of therapy), and assignment to nivolumab (yes vs. no) as covariates.
    measure
    Proportion of positive positron emission tomography (PET) scans
    time Frame
    Up to 6 cycle (1 cycle = 21 days)
Full study description
brief Summary
This phase III trial compares the effects of nivolumab with chemo-immunotherapy versus chemo-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 cancer cells to grow and spread. Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them 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. This may help the immune system kill cancer cells. Giving nivolumab with chemo-immunotherapy may help treat patients with PMBCL.
detailed Description
PRIMARY OBJECTIVE: I. To determine if nivolumab + chemo-immunotherapy results in a superior long term progression-free survival (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. SECONDARY OBJECTIVES: I. To compare the rates of "efficacy-related event-free survival (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. II. 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. III. To compare the rates of overall survival (OS) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL. IV. To establish the rate of a positive positron emission tomography (PET)-computed tomography (CT) (defined as Deauville score 4 or 5) at the completion of 6 cycles of nivolumab + rituximab (R)- cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/dose-adjusted (DA)-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)-R and R-CHOP/DA-EPOCH-R in patients with newly diagnosed PMBCL and evaluate the prognostic significance of such a finding. EXPLORATORY OBJECTIVES: I. To bank radiology images for further studies. II. To bank specimens for future correlative studies. III. Characterize the immune profile of patients treated with nivolumab + chemo-immunotherapy to identify markers predictive of response. IV. Define the rate of complete response at the completion of initial planned therapy. OUTLINE: 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 versus \[vs.\] R-CHOP vs. R-CHOP + RT) and whether or not the patient had 1 prior cycle of therapy. ARM A (DA-EPOCH-R): Patients receive prednisone or prednisolone orally (PO) once daily (QD) on days 1-5 and rituximab intravenously (IV) or rituximab and hyaluronidase human subcutaneously (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 and cyclophosphamide IV over 30-60 minutes on day 5. Beginning 24-72 hours after completing cyclophosphamide, patients receive filgrastim or pegylated filgrastim SC daily until absolute neutrophil count (ANC) is \>= 500/uL after the expected nadir. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) during screening and as clinically indicated and a lumbar puncture (LP) for cerebral spinal fluid (CSF) collection optionally during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study. ARM B (DA-EPOCH-R + NIVOLUMAB): Patients receive treatment as in Arm A. Patients also receive nivolumab IV over 30 minutes on day 1. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study. ARM C (R-CHOP): Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5. Patients also receive cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 1-15 minutes 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 treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study. ARM D (R-CHOP + NIVOLUMAB): Patients receive treatment as in Arm C. Patients also receive nivolumab IV over 30 minutes on day 1. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study. ARM E (R-CHOP + RADIOTHERAPY): Patients receive treatment as in Arm C. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection 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 undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study. After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and annually thereafter.
Source references
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-d8572ca3e49f65ad8060
      requested nct id
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      primary nct id
      NCT04759586
      source kind
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      source record id
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      true
      id
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      nct id
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      occurrences
      1. context exact
        r institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1802"><li><strong><a href="/clinicaltrials/NCT04759586">ANHL1931 (NCT04759586)</a></strong> (Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphom
        end
        237560
        exact text
        NCT04759586
        start
        237549
      2. context exact
        l trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1802"><li><strong><a href="/clinicaltrials/NCT04759586">ANHL1931 (NCT04759586)</a></strong> (Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma)<strong>:</strong> Th
        end
        237583
        exact text
        NCT04759586
        start
        237572
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/fd36e5abb88f40b91c.html
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      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:02.430571+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      82ec317f50f4df507988e345c98b7f250d282967704c0ba2eddd7b442373575f
      source title
      Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 17, 2025
        datetime
        2025-04-17T12:00:00Z
        display
        April 17, 2025

    Preserved source evidence · Not medical advice