Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL (MTR²)

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

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

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Tafasitamab; Drug: Lenalidomide; Drug: Rituximab; Drug: Methotrexate

Detailed Description

This is a single-arm, prospective, multicenter, single-stage phase-II trial for patients aged 18-69 years with ECOG PS ≥2 or ≥70 years with previously untreated PCNSL, who are not eligible for HCT-ASCT at investigators decision. This trial evaluates the CRR rate after at least 2 cycles of MTR2, the incidence and severity of adverse events, progression-free survival, and overall survival after one year.

It is planned to enroll eligible patients with PCNSL, i.e. who receive at least 2 cycles of the combination of rituximab, MTX and the IMPs tafasitamab and lenalidomide, over a one-year period. Follow-up will be conducted for 1 year within the trial.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peter Borchmann, Prof. Dr. med.; Phone Number: 88180 +49221478; Email: MTR2-Studienteam@uk-koeln.de
• Study Contact Backup: Name: Jan Michel Heger, Dr. med.; Phone Number: 39221 +49221478; Email: MTR2-Studienteam@uk-koeln.de

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Not yet recruiting
    • Charité - Universitätsmedizin Berlin
    • Contact: Stefan Habringer, Dr.; Email: stefan.habringer@charite.de
    • Contact: Björn Chapuy, Prof. Dr.; Phone Number: 613423 +49030450; Email: bioern.chapuy@charite.de
  • Cologne, Germany, 50937
    • Not yet recruiting
    • University of Cologne
    • Contact: Peter Borchmann, Prof. Dr. med.; Phone Number: 88180 +49 221 478; Email: MTR2-Studientean@uk-koeln.de
    • Contact: Jan Michel Heger, Dr. med.; Phone Number: 39221 +49221478; Email: MTR2-Studientean@uk-koeln.de
  • Baden-Würtemberg
    • Freiburg, Baden-Würtemberg, Germany, 79106
      • Not yet recruiting
      • Universitätsklinikum Freiburg
      • Contact: Elisabeth Schorb, PD Dr. med.; Phone Number: 35360 +49761270; Email: elisabeth.schorb@uniklinik-freiburg.de
      • Contact: Eliza Lauer, Dr. med.; Email: eliza.lauer@uniklinik-freiburg.de
  • Baden-Württemberg
    • Stuttgart, Baden-Württemberg, Germany, 70174
      • Recruiting
      • Klinikum Stuttgart - Katharienenhospital
      • Contact: Gerald Illerhaus, Prof. Dr.; Phone Number: 30456 +49711278; Email: g.illerhaus@klinikum-stuttgart.de
      • Contact: Claudia Fest, Dr.; Email: c.fest@klinikum-stuttgart.de
  • Hamurg
    • Hamburg, Hamurg, Germany, 20246
      • Not yet recruiting
      • Universitätsklinikum Hamburg-Eppendorf
      • Contact: Minna Voigtländer, Dr. med.; Phone Number: +49407410; Email: m.voigtlaender@uke.de
      • Contact: Winfried Alsdorf, Dr. med.
  • Nordrhein Westphalen
    • Essen, Nordrhein Westphalen, Germany, 45147
      • Not yet recruiting
      • Universitätsklinikum Essen
      • Contact: Bastian Tresckow, PD Dr. med.; Phone Number: 2421 +49201723; Email: bastian.tresckow@uk-essen.de
      • Contact: Karl Richard Maria Noppeney, Dr. med.; Phone Number: 6120 +49201723

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-69 years with ECOG PS ≥2 or age ≥70 years, and ineligible for HCT-ASCT as per investigators discretion
2. 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
3. At least one measurable lesion

4. 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%
   • Adequate pulmonary function as per investigators discretion
5. Written, signed, and dated informed consent for the trial provided by the participant
6. Female persons are eligible to participate if they are post-menopausal or females of no childbearing potential or if they agree to use a method of contraception considered safe described in Section 12.1.2.1.
7. Male persons with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods as described in Section 12.1.2.2.

Exclusion Criteria:

1. 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
2. Systemic lymphoma manifestation outside the CNS
3. Diagnosis of previous Non-Hodgkin lymphoma at any time
4. Primary vitreoretinal or leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord
5. HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and / or presence of RNA confirmed by PCR

6. 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
7. Hypersensitivity to study treatment or any component of the formulation
8. Stomatitis or gastrointestinal ulcerations preventing the use of methotrexate
9. Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR
10. Severe active infection
11. Congenital or acquired immunodeficiency including previous organ transplantation
12. Pregnant or nursing (lactating) women.
13. Lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate their own wishes correspondingly

14. Non-compliance, for reasons including, but not limited to the following:

    1. Increased alcohol consumption, drug dependency or substance abuse that would interfere with cooperation with requirements of the trial
    2. Refusal of blood products during treatment
    3. Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible
15. Relationship of dependence or employer-employee relationship to the sponsor or the investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: combination of Tafasitamab (Minjuvi®), Lenalidomide, Rituximab and Methotrexate; 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; IV; Drug: Lenalidomide; Oral; Drug: Rituximab; IV; Drug: Methotrexate; IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response rate (BORR)	is defined as the rate of patients having achieved a CR or PR according to at least one post-baseline tumor assessment	At the end of cycle 4 (each cycle is 21 days)
Progression-free survival (PFS)	will be calculated for each patient as time between the start of treatment with MTR2 and the date of first progression, relapse or death or, in cases of continuing response, the date of the last documented follow-up (FU-CRF or written medical report).	After 1 year
Overall survival (OS)	will be calculated for each patient as time between the start of treatment with MTR2 and the date of death or the date of the last documented follow-up (FU-CRF or written medical report).	After 1 year
Incidence and severity of adverse events	Incidence and severity of adverse events, including toxic deaths during induction therapy will be summarized based on CTCAE grades	during induction therapy

Collaborators and Investigators

• Sponsor: University of Cologne
• Collaborators: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Rituximab; Methotrexate
• Other Study ID Numbers: Uni-Köln-4968

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
• product manufactured in and exported from the U.S.: No