Multicenter Study of Safety and Efficacy Nivolumab at the Fixed Dose 40 mg (Nivo40) in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed PMBL

National Research Center for Hematology, Russia

Status and phase: Enrolling; Phase 3

Conditions: Primary Mediastinal Lymphoma

Treatments: Drug: Prednisolone; Drug: Doxorubicin Hydrochloride; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Nivolumab 40 mg in 4 ml Injection; Drug: Etoposide Phosphate; Drug: Filgrastim; Drug: Vincristine Sulfate; Drug: Pegfilgrastim

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT06188676

PMBL-2022

Details and patient eligibility

About

This compares the effects of nivolumab at a fixed dose of 40 mg 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria Age 18-70 years old Ejection fraction greater than 50% ECOG 0-2 status Signed informed consent No severe concurrent illness measurable disease (at least one lesion that can be accurately measured in at least two dimensions on a CT scan, at least >15 mm in largest diameter

Exclusion criteria

• Uncontrolled bacterial or fungal infection at the time of enrollment
• Requirement for vasopressor support at the time of enrollment
• Severe organ failure: creatinine more than 2 norms; ALT, AST more than 5 norms; bilirubin more than 1.5 norms
• Karnofsky index <30%
• Pregnancy
• Somatic or psychiatric disorder making the patient unable to sign an informed consent
• Active or prior documented autoimmune disease requiring systemic treatment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

A

Active Comparator group

Description:

Active Comparator: Arm A (DA-EPOCH-R) Patients receive prednisone or prednisolone on days 1-5 and rituximab IV or rituximab and hyaluronidase human 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 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses

Treatment:

Drug: Rituximab

Drug: Vincristine Sulfate

Drug: Pegfilgrastim

Drug: Etoposide Phosphate

Drug: Prednisolone

Drug: Doxorubicin Hydrochloride

Drug: Filgrastim

Drug: Cyclophosphamide

B

Experimental group

Description:

(DA-EPOCH-R, nivolumab) Patients receive treatment as in Arm A. Patients also receive nivolumab 40 mg 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 also undergo FDG-PET/CT on study. When СR is achieved according to PET / CT after 4 cycles of chemotherapy, 2 randomization is performed, a total of 4 or 6 chemotherapy courses.

Treatment:

Drug: Rituximab

Drug: Vincristine Sulfate

Drug: Pegfilgrastim

Drug: Etoposide Phosphate

Drug: Prednisolone

Drug: Doxorubicin Hydrochloride

Drug: Filgrastim

Drug: Nivolumab 40 mg in 4 ml Injection

Drug: Cyclophosphamide