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

NCT06188676 | Recruiting Phase 3

• 1 other identifier: PMBL-2022
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Primary Mediastinal Lymphoma

Keywords

PET-adapted Treatment; Nivolumab at the fixed dose 40 mg; R-DA-EPOCH

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  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.

  From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 5 years

Secondary Outcomes (3)

• Efficacy-related event-free survival

  Up to 5 years

• Therapy-related event-free survival

  Up to 5 years

• Overall survival

  Up to 5 years

Study Arms (2)

A

ACTIVE COMPARATOR

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

Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Etoposide Phosphate; Drug: Prednisolone; Drug: Rituximab; Drug: Vincristine Sulfate; Drug: Filgrastim; Drug: Pegfilgrastim

B

EXPERIMENTAL

(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.

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

Interventions

Cyclophosphamide DRUG

Ciclofosfamida

A; B

Doxorubicin Hydrochloride DRUG

Adriamycin

A; B

Etoposide Phosphate DRUG

Etopophos

A; B

Prednisolone DRUG

Prednisolonum

A; B

Rituximab DRUG

Chimeric Anti-CD20 Antibody

A; B

Vincristine Sulfate DRUG

Oncovin

A; B

Filgrastim DRUG

G-CSF

A; B

Pegfilgrastim DRUG

PEG-filgrastim

A; B

Nivolumab 40 mg in 4 ml Injection DRUG

Opdivo

B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Research Center for Hematology, Russia: lead

Study Sites (1)

National Research Center for Hematology

Moscow, 125167, Russia

RECRUITING

MeSH Terms

Interventions

Cyclophosphamide; Doxorubicin; etoposide phosphate; Prednisolone; Rituximab; Vincristine; Filgrastim; pegfilgrastim; Nivolumab; Injections

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Antibodies, Monoclonal, Humanized; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Elena Parovichnikova, MD,PhD

  Nathional Medical Research Center for Hematology Moscow Russia 125167

  STUDY DIRECTOR

Central Study Contacts

Yana Mangasarova, MD

CONTACT

+74956122361; v.k.jana@mail.ru

Euvgena Zvonkov, MD,PhD

CONTACT

+74956122361; dr.zvonkov@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director Nathional Medical Research Center for Hematology Moscow Russia

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: January 3, 2024
• Study Start: April 1, 2022
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: January 3, 2024

Record last verified: 2023-12

Locations

RU (1)