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

Primary Purpose

Non-Hodgkin Lymphoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Tafasitamab
Lenalidomide
Rituximab
Methotrexate
Sponsored by
University of Cologne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients aged 18-69 years with ECOG PS ≥2 or ≥70 years 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) ≥ 60 ml/min

    • Adequate hepatic function, defined as:

      • ALAT and ASAT ≤ 5 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 must be obtained prior to participation in the study
  6. Male participants with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods.

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. Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR
  9. Congenital or acquired immunodeficiency including previous organ transplantation
  10. Pregnant or nursing (lactating) women and women who are not confirmed to be menopausal / post-menopausal.
  11. Patient's lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate his / her own wishes correspondingly

  12. Non-compliance, e.g. due to

    • Drug dependency or substance abuse that would interfere with cooperation with requirements of the trial
    • Refusal of blood products during treatment
    • Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible
  13. Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator

Sites / Locations

  • University of Cologne

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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).
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).
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

Full Information

First Posted
August 2, 2022
Last Updated
May 2, 2023
Sponsor
University of Cologne
Collaborators
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05583071
Brief Title
Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL
Acronym
MTR²
Official Title
Pilot-trial of Methotrexate, Tafasitamab (Minjuvi®), Lenalidomide (Revlimid®) and Rituximab in Patients Ineligible for HCT-ASCT With Primary Central Nervous System Lymphoma (PCNSL)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cologne
Collaborators
Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
single-arm, prospective, multicenter, single-stage phase-II trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
combination of Tafasitamab (Minjuvi®), Lenalidomide, Rituximab and Methotrexate
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tafasitamab
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
IV
Primary Outcome Measure Information:
Title
complete response rate (CRR)
Description
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.
Time Frame
At the end of cycle 2 (each cycle is 21 days)
Secondary Outcome Measure Information:
Title
Best overall response rate (BORR)
Description
is defined as the rate of patients having achieved a CR or PR according to at least one post-baseline tumor assessment
Time Frame
At the end of cycle 4 (each cycle is 21 days)
Title
Progression-free survival (PFS)
Description
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).
Time Frame
After 1 year
Title
Overall survival (OS)
Description
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).
Time Frame
After 1 year
Title
Incidence and severity of adverse events
Description
Incidence and severity of adverse events, including toxic deaths during induction therapy will be summarized based on CTCAE grades
Time Frame
during induction therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged 18-69 years with ECOG PS ≥2 or ≥70 years 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) ≥ 60 ml/min Adequate hepatic function, defined as: ALAT and ASAT ≤ 5 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 Written, signed, and dated informed consent must be obtained prior to participation in the study Male participants with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods. Exclusion Criteria: 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 Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR Congenital or acquired immunodeficiency including previous organ transplantation Pregnant or nursing (lactating) women and women who are not confirmed to be menopausal / post-menopausal. Patient's lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate his / her own wishes correspondingly Non-compliance, e.g. due to Drug dependency or substance abuse that would interfere with cooperation with requirements of the trial Refusal of blood products during treatment Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Borchmann, Prof. Dr. med.
Phone
+49221478
Ext
88180
Email
MTR2-Studienteam@uk-koeln.de
First Name & Middle Initial & Last Name or Official Title & Degree
Jan Michel Heger, Dr. med.
Phone
+49221478
Ext
39221
Email
MTR2-Studienteam@uk-koeln.de
Facility Information:
Facility Name
University of Cologne
City
Cologne
ZIP/Postal Code
50937
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Borchmann, Prof. Dr. med.
Phone
+49 221 478
Ext
88180
Email
MTR2-Studientean@uk-koeln.de
First Name & Middle Initial & Last Name & Degree
Jan Michel Heger, Dr. med.
Phone
+49221478
Ext
39221
Email
MTR2-Studientean@uk-koeln.de

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL

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