RL-MPV Followed by BBC HCT Using Autologous Stem Cells and Maintenance Therapy With Nivolumab for Newly Diagnosed PCNSL

NCT05425654 | Recruiting Phase 2

• 1 other identifier: "CNS-2021"
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the efficacy and safety of the new treatment proposed in this study. Conducting a prospective study "CNS-2015" in patients with PDLBCL CNS made it possible to achieve 2-year EFS, DFS and OS of 83%, 83% and 88%, respectively. The presence of early relapses of the disease has now led to the need to find an alternative program for patients with PDLBCL CNS. In the new "CNS-2021" protocol, lenalidomide was included in the R-MPV program in order to intensify the induction stage. In the conditioning regimen, thiotepa was replaced by carmustine, due to its significant CNS bioavailability. In order to possibly prevent early relapses, an anti-PD-1 inhibitor (nivolumab) was used as maintenance therapy.

Conditions

Primary CNS Lymphoma

Outcome Measures

Primary Outcomes (1)

• frequency of adverse events

  to evaluate the frequency of adverse events (safety and efficacy) of the use of RL-MPV followed by high-dose chemotherapy using carmustine, cyclophosphamide and busulfan with stem cell rescue in patients with newly diagnosed PCSNL.

  Time Frame: 1-year event-free survival and acute treatment-related toxicity.]

Secondary Outcomes (1)

• response rates

  Time Frame: after 56 days (after 4 cycles - each cycle is equal to 14 days)

Study Arms (1)

RL-MPV + BBC/auto-HCT+ nivolumab

EXPERIMENTAL

Rituximab, methotrexate (MTX), procarbazine, vincristine and lenalidomide (RL-MPV). The peripheral blood stem cell (PBSC) harvest procedure will be performed after 2nd cycle of RL-MPV. High dose chemotherapy Busulfan, Thiotepa, and Cyclophosphamide. 3 months after auto-HSCT, maintenance therapy with nivolumab 3 mg/kg is started for 6 months every 2 weeks

Drug: Rituximab, Methotrexate, Vincristine, Procarbazine, Lenalidomide

Interventions

Rituximab, Methotrexate, Vincristine, Procarbazine, Lenalidomide DRUG

The initial treatment will consist of cycles of 14 days. Each cycle will start with rituximab, which will be given by vein on day 1. On day 2 you will receive: Methotrexate will be given by vein over 2 to 3 hours and vincristine will be given as a single injection over a few minutes. Procarbazine and Lenalidomide are a pill that you will take at bedtime for 7 nights starting on day 2. Procarbazine and Lenalidomide are only given every other cycle. During each cycle, you will be in the hospital. After the second cycle of chemotherapy, PBPCs will be collected. You will be hospitalized again for high-dose chemotherapy and receive supportive medications to help avoid complications, including antibiotics and blood transfusions. Busulfan, carmustine and cyclophosphamide will be given to you for 5 days. After break of 1 day, we will return your PBPC (or bone marrow) to you through a vein. You will be in the hospital for at least 3 weeks.

Also known as: Busulfan, Carmustine, and Cyclophosphamide

RL-MPV + BBC/auto-HCT+ nivolumab

Eligibility Criteria

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

You may qualify if:

• All patients must have non-Hodgkin's lymphoma involving the brain, as demonstrated by CT or MRI and histologic confirmation by one of the following: A positive CSF cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers.
• A biopsy of the vitreous or uvea demonstrating non-Hodgkin's lymphoma. Brain biopsy.
• Patients must be HIV-1 negative. Patient must have left ventricular ejection fraction ≥ 50%. Patients must have no evidence of systemic lymphoma. This must be demonstrated by a CT scan of the chest, abdomen and pelvis prior to registration.
• Patients must have adequate bone marrow function (defined as peripheral leucocyte count \>3000 cells/mm3 and platelet count \> 100,000 cells/mm3), liver function (bilirubin \< 2.0 mg/%), and adequate renal function (serum creatinine \< 1.5 mg/dl or creatinine clearance \> 50cc/min/1.73M2).
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
• Patients must be between 18 and 70years-old. Patients must sign an informed consent.

You may not qualify if:

• Prior cranial irradiation Other active primary malignancy. Pre-existing immunodeficiency such as renal transplant recipient. Prior treatment with chemotherapy for CNS lymphoma.

Sponsors & Collaborators

• National Research Center for Hematology, Russia: lead

Study Sites (1)

Nathional Medical Research Center for Hematology

Moscow, 125167, Russia

RECRUITING

MeSH Terms

Interventions

Rituximab; Methotrexate; Vincristine; Procarbazine; Lenalidomide; Busulfan; Carmustine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phthalimides; Phthalic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrosourea Compounds; Urea; Nitroso Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Eugene Zvonkov, Phd, MD

CONTACT

+7 (495) 612-13-31; dr.zvonkov@mail.ru

Daria Koroleva, Phd

CONTACT

+7 (495) 612-13-31; koroleva_12-12@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 21, 2022
• Study Start: May 17, 2021
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2026
• Last Updated: June 21, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)