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

Primary CNS Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05425654
• Other study ID #: "CNS-2021"
• Status: Recruiting
• Phase: Phase 2
• Start date: May 17, 2021
• Est. completion date: May 2026

Study information

• Verified date: June 2022
• Source: National Research Center for Hematology, Russia
• Contact: Eugene Zvonkov, Phd, MD
• Phone: +7 (495) 612-13-31
• Email: dr.zvonkov[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 2026
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Primary CNS Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Russian Federation	Nathional Medical Research Center for Hematology	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
National Research Center for Hematology, Russia

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	response rates	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)