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

Primary Purpose

Primary CNS Lymphoma

Status

Recruiting

Phase

Phase 2

Locations

Russian Federation

Study Type

Interventional

Intervention

Rituximab, Methotrexate, Vincristine, Procarbazine, Lenalidomide

About this trial

This is an interventional treatment trial for Primary CNS Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Nathional Medical Research Center for HematologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RL-MPV + BBC/auto-HCT+ nivolumab

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

response rates

to evaluate response rates with the combination of lenalidomide and R-MPV as induction chemotherapy.

Full Information

NCT ID

NCT05425654

First Posted

June 8, 2022

Last Updated

June 16, 2022

Sponsor

National Research Center for Hematology, Russia

1. Study Identification

Unique Protocol Identification Number

NCT05425654

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 17, 2021 (Actual)

Primary Completion Date

May 2023 (Anticipated)

Study Completion Date

May 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Research Center for Hematology, Russia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary CNS Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

RL-MPV + BBC/auto-HCT+ nivolumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rituximab, Methotrexate, Vincristine, Procarbazine, Lenalidomide

Other Intervention Name(s)

Busulfan, Carmustine, and Cyclophosphamide

Intervention Description

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.

Primary Outcome Measure Information:

Title

frequency of adverse events

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

response rates

Description

to evaluate response rates with the combination of lenalidomide and R-MPV as induction chemotherapy.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Eugene Zvonkov, Phd, MD

Phone

+7 (495) 612-13-31

dr.zvonkov@mail.ru

First Name & Middle Initial & Last Name or Official Title & Degree

Daria Koroleva, Phd

Phone

+7 (495) 612-13-31

koroleva_12-12@mail.ru

Facility Information:

Facility Name

Nathional Medical Research Center for Hematology

City

Moscow

ZIP/Postal Code

125167

Country

Russian Federation

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Eugene Zvonkov, PhD/MD

Phone

+7 (495) 612-13-31

dr.zvonkov@mail.ru

First Name & Middle Initial & Last Name & Degree

Daria Koroleva, PhD

Phone

+ 7 (964) 717-53-12

koroleva_12-12@mail.ru

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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