Official Title
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
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.
Trial Description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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.
- To compare the rates of overall survival (OS) between
chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with
newly diagnosed PMBCL.
- 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:
- To bank radiology images for further studies.
- To bank specimens for future correlative studies.
- Characterize the immune profile of patients treated with
nivolumab + chemo-immunotherapy to identify markers predictive of response.
- 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 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.
ARM B (DA-EPOCH-R + NIVOLUMAB): Patients receive treatment
as in Arm A. Patients also receive nivolumab IV over 30 minutes on day 1.
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.
ARM D (R-CHOP + NIVOLUMAB): Patients receive treatment as in
Arm C. Patients also receive nivolumab IV over 30 minutes on day 1.
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.
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.
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.
View this trial on ClinicalTrials.gov
