MTR²: Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL

• Sponsor: University of Cologne (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05583071
• Collaborator: Incyte Corporation (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 37.9
• Patients Per Site Per Month: 0.5

Study Details

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)

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma	Drug: Tafasitamab; Drug: Lenalidomide; Drug: Rituximab; Drug: Methotrexate	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: single-arm, prospective, multicenter, single-stage phase-II trialsingle-arm, prospective, multicenter, single-stage phase-II trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Anticipated Study Start Date: Jan 1, 2023
• Anticipated Primary Completion Date: Jan 1, 2026
• Anticipated Study Completion Date: Mar 1, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. complete response rate (CRR) [At the end of cycle 2 (each cycle is 21 days)]

   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

1. Best overall response rate (BORR) [At the end of cycle 4 (each cycle is 21 days)]

   is defined as the rate of patients having achieved a CR or PR according to at least one post-baseline tumor assessment

2. Progression-free survival (PFS) [After 1 year]

   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).

3. Overall survival (OS) [After 1 year]

   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).

4. Incidence and severity of adverse events [during induction therapy]

   Incidence and severity of adverse events, including toxic deaths during induction therapy will be summarized based on CTCAE grades

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Written, signed, and dated informed consent must be obtained prior to participation in the study

2. 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

1. Hypersensitivity to study treatment or any component of the formulation

2. Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR

3. Congenital or acquired immunodeficiency including previous organ transplantation

4. Pregnant or nursing (lactating) women and women who are not confirmed to be menopausal / post-menopausal.

5. 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

6. 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

1. Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cologne	Cologne		Germany	50937

Sponsors and Collaborators

• University of Cologne
• Incyte Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prof. Dr. Peter Borchmann, Trial Chairman, University of Cologne
• ClinicalTrials.gov Identifier: NCT05583071
• Other Study ID Numbers: Uni-Köln-4968
• First Posted: Oct 17, 2022
• Last Update Posted: Oct 17, 2022
• Last Verified: Oct 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Rituximab; Methotrexate; Lenalidomide

Study Results

No Results Posted as of Oct 17, 2022