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Active Not RecruitingNCT04759586

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

A Randomized Phase 3 Trial of Nivolumab (NSC# 748726) in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma

Status
Active Not Recruiting
Phase
Phase 3
Study type
Interventional
Enrollment
244 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
2 Years
Healthy volunteers
Not accepted

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.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo blood and CSF sample collection
PROCEDUREBone Marrow AspirationUndergo bone marrow biopsy and aspiration
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy and aspiration
PROCEDUREComputed TomographyUndergo CT or PET/CT
DRUGCyclophosphamideGiven IV
DRUGDoxorubicin HydrochlorideGiven IV
PROCEDUREEchocardiography TestUndergo ECHO
DRUGEtoposide PhosphateGiven IV
BIOLOGICALFilgrastimGiven SC
PROCEDURELumbar PunctureUndergo LP
BIOLOGICALNivolumabGiven IV
BIOLOGICALPegfilgrastimGiven SC
PROCEDUREPositron Emission TomographyUndergo PET/CT
DRUGPrednisoloneGiven PO
DRUGPrednisoneGiven PO
RADIATIONRadiation TherapyUndergo radiation therapy
BIOLOGICALRituximabGiven IV
BIOLOGICALRituximab and Hyaluronidase HumanGiven SC
DRUGVincristine SulfateGiven IV

Timeline

Start date
2021-10-05
Primary completion
2026-12-31
Completion
2026-12-31
First posted
2021-02-18
Last updated
2026-04-13

Locations

233 sites across 4 countries: United States, Australia, Canada, Puerto Rico

Regulatory

Source: ClinicalTrials.gov record NCT04759586. Inclusion in this directory is not an endorsement.