Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL

NCT05583071 | Recruiting Phase 2 DMC

• 1 other identifier: Uni-Köln-4968
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 6

Brief Summary

Pilot-trial of Methotrexate, Tafasitamab (Minjuvi®), Lenalidomide (Revlimid®) and Rituximab in patients ineligible for HCT-ASCT with Primary Central Nervous System Lymphoma (PCNSL)

Conditions

Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• complete response rate (CRR)

  The CRR will be determined by IRC and according to IPCG criteria. This endpoint reflects the proportion of patients who can potentially proceed to different consolidation or maintenance strategies to achieve durable responses.

  At the end of cycle 2 (each cycle is 21 days)

Secondary Outcomes (4)

• Best overall response rate (BORR)

  At the end of cycle 4 (each cycle is 21 days)

• Progression-free survival (PFS)

  After 1 year

• Overall survival (OS)

  After 1 year

• Incidence and severity of adverse events

  during induction therapy

Study Arms (1)

combination of Tafasitamab (Minjuvi®), Lenalidomide, Rituximab and Methotrexate

EXPERIMENTAL

All patients will receive tafasitamab (Minjuvi®) 12 mg/KG body weight and rituximab 375 mg/m² on days 0 and 5, followed by methotrexate 3,5 g/m² on day 1 as an intravenous infusion. Lenalidomide will be administered orally at 20 mg/day during the first cycle and at 25 mg/day during subsequent cycles on days 4-17 of each 21-day cycle for a total number of 4 cycles. The treatment duration per patient will be 84 days.

Drug: Tafasitamab; Drug: Lenalidomide; Drug: Rituximab; Drug: Methotrexate

Interventions

Tafasitamab DRUG

IV

combination of Tafasitamab (Minjuvi®), Lenalidomide, Rituximab and Methotrexate

Lenalidomide DRUG

Oral

combination of Tafasitamab (Minjuvi®), Lenalidomide, Rituximab and Methotrexate

Rituximab DRUG

IV

combination of Tafasitamab (Minjuvi®), Lenalidomide, Rituximab and Methotrexate

Methotrexate DRUG

IV

combination of Tafasitamab (Minjuvi®), Lenalidomide, Rituximab and Methotrexate

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-69 years with ECOG PS ≥2 or age ≥70 years, and ineligible for HCT-ASCT as per investigators discretion
• Previously untreated, histologically (or cytologically) confirmed diagnosis of primary B-cell lymphoma of the central nervous system (PCNSL) by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
• At least one measurable lesion
• Adequate organ function:
• Adequate kidney function, defined as:
• Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 50 ml/min
• Adequate hepatic function, defined as:
• ALAT and ASAT ≤ 3 ULN
• Bilirubin ≤ 2.0 mg/dl (except for Meulengracht disease)
• Adequate bone marrow function, defined as:
• White blood cell (WBC) count ≥ 3000/µL or absolute neutrophil count (ANC) ≥ 1000/µL
• Platelets ≥ 50.000/µL
• Hemoglobin \> 8.0 g/dl
• Adequate cardiac function, defined as:
• Cardiac ejection fraction ≥ 40%

You may not qualify if:

• Prior treatment for PCNSL with the exception of a pre-phase treatment comprising steroid treatment and / or single application of rituximab 375 mg/m² and methotrexate 3.5 g/m²
• Systemic lymphoma manifestation outside the CNS
• Diagnosis of previous Non-Hodgkin lymphoma at any time
• Primary vitreoretinal or leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord
• HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and / or presence of RNA confirmed by PCR
• Previous or concurrent malignancies with the following exceptions:
• Surgically cured carcinoma in-situ
• Other kinds of cancer without evidence of disease for at least 5 years
• Hypersensitivity to study treatment or any component of the formulation
• Stomatitis or gastrointestinal ulcerations preventing the use of methotrexate
• Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR
• Severe active infection
• Congenital or acquired immunodeficiency including previous organ transplantation
• Pregnant or nursing (lactating) women.
• Lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate their own wishes correspondingly

Sponsors & Collaborators

• University of Cologne: lead
• Incyte Corporation: collaborator

Study Sites (6)

Klinikum Stuttgart - Katharienenhospital

Stuttgart, Baden-Wurttemberg, 70174, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Würtemberg, 79106, Germany

NOT YET RECRUITING

University of Cologne

Cologne, Germany, 50937, Germany

NOT YET RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Hamurg, 20246, Germany

NOT YET RECRUITING

Universitätsklinikum Essen

Essen, Nordrhein Westphalen, 45147, Germany

NOT YET RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 12203, Germany

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

tafasitamab; Lenalidomide; Rituximab; Methotrexate

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines

Central Study Contacts

Peter Borchmann, Prof. Dr. med.

CONTACT

+49221478; MTR2-Studienteam@uk-koeln.de

Jan Michel Heger, Dr. med.

CONTACT

+49221478; MTR2-Studienteam@uk-koeln.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Trial Chairman

Model Details: single-arm, prospective, multicenter, single-stage phase-II trial

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: October 17, 2022
• Study Start: August 23, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6)