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

NCT ID: NCT06188676

Last Updated: 2024-01-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-01

Study Completion Date

2029-04-01

Brief Summary

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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.

Detailed Description

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Conditions

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Primary Mediastinal Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A

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

Group Type ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type DRUG

Ciclofosfamida

Doxorubicin Hydrochloride

Intervention Type DRUG

Adriamycin

Etoposide Phosphate

Intervention Type DRUG

Etopophos

Prednisolone

Intervention Type DRUG

Prednisolonum

Rituximab

Intervention Type DRUG

Chimeric Anti-CD20 Antibody

Vincristine Sulfate

Intervention Type DRUG

Oncovin

Filgrastim

Intervention Type DRUG

G-CSF

Pegfilgrastim

Intervention Type DRUG

PEG-filgrastim

B

(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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Ciclofosfamida

Doxorubicin Hydrochloride

Intervention Type DRUG

Adriamycin

Etoposide Phosphate

Intervention Type DRUG

Etopophos

Prednisolone

Intervention Type DRUG

Prednisolonum

Rituximab

Intervention Type DRUG

Chimeric Anti-CD20 Antibody

Vincristine Sulfate

Intervention Type DRUG

Oncovin

Filgrastim

Intervention Type DRUG

G-CSF

Pegfilgrastim

Intervention Type DRUG

PEG-filgrastim

Nivolumab 40 mg in 4 ml Injection

Intervention Type DRUG

Opdivo

Interventions

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Cyclophosphamide

Ciclofosfamida

Intervention Type DRUG

Doxorubicin Hydrochloride

Adriamycin

Intervention Type DRUG

Etoposide Phosphate

Etopophos

Intervention Type DRUG

Prednisolone

Prednisolonum

Intervention Type DRUG

Rituximab

Chimeric Anti-CD20 Antibody

Intervention Type DRUG

Vincristine Sulfate

Oncovin

Intervention Type DRUG

Filgrastim

G-CSF

Intervention Type DRUG

Pegfilgrastim

PEG-filgrastim

Intervention Type DRUG

Nivolumab 40 mg in 4 ml Injection

Opdivo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Research Center for Hematology, Russia

NETWORK

Sponsor Role lead

Responsible Party

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Elena N.Parovichnikova

Vice-director Nathional Medical Research Center for Hematology Moscow Russia

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Elena Parovichnikova, MD,PhD

Role: STUDY_DIRECTOR

Nathional Medical Research Center for Hematology Moscow Russia 125167

Locations

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National Research Center for Hematology

Moscow, , Russia

Site Status RECRUITING

Countries

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Russia

Central Contacts

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Yana Mangasarova, MD

Role: CONTACT

+74956122361

Euvgena Zvonkov, MD,PhD

Role: CONTACT

+74956122361

Facility Contacts

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Yana Mangasarova, MD

Role: primary

+74956122361

Other Identifiers

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PMBL-2022

Identifier Type: -

Identifier Source: org_study_id

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