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

June 16, 2022 updated by: National Research Center for Hematology, Russia

Rituximab, Methotrexate, Procarbazine, Vincristine, Lenalidomide (RL-MPV) Followed by BBC (BCNU, Busulfan, Cyclophosphamide) High-dose Chemotherapy With Auto-HCT and Maintenance Therapy With Nivolumab in Newly Diagnosed Primary CNS Lymphoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients will receive 4 cycles of RL-MPV (rituximab, methotrexate (MTX), procarbazine, vincristine, and lenalidomide (RL-MPV) as induction. The conditioning regimen prior to autologous blood stem cell transplantation includes high doses busulfan, thiotepa, and cyclophosphamide. After 3 months after autologous blood stem cell transplantation, maintenance therapy with nivolumab 3 mg/kg every 2 weeks for 6 months will be started.Patients will be out of the study at the time of death. All patients believe in the possibility of survival within 3 months throughout their lives. Survival status can be obtained by phone call, storage visit, or medical records (eg doctor's note/lab results from a clinic or storage visit).

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Eugene Zvonkov, Phd, MD
  • Phone Number: +7 (495) 612-13-31
  • Email: dr.zvonkov@mail.ru

Study Contact Backup

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 125167
        • Recruiting
        • Nathional Medical Research Center for Hematology
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RL-MPV + BBC/auto-HCT+ nivolumab
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
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.
Other Names:
  • Busulfan, Carmustine, and Cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
frequency of adverse events
Time Frame: Time Frame: 1-year event-free survival and acute treatment-related toxicity.]
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
response rates
Time Frame: Time Frame: after 56 days (after 4 cycles - each cycle is equal to 14 days)
to evaluate response rates with the combination of lenalidomide and R-MPV as induction chemotherapy.
Time Frame: after 56 days (after 4 cycles - each cycle is equal to 14 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Research Center for Hematology, Russia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2021

Primary Completion (Anticipated)

May 1, 2023

Study Completion (Anticipated)

May 1, 2026

Study Registration Dates

First Submitted

June 8, 2022

First Submitted That Met QC Criteria

June 16, 2022

First Posted (Actual)

June 21, 2022

Study Record Updates

Last Update Posted (Actual)

June 21, 2022

Last Update Submitted That Met QC Criteria

June 16, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • "CNS-2021"

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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