MTR²

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Cologne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

24 Jun 2024 → ongoing

Decision date (initial)

2023-11-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Incyte GmbH

External identifiers

EU CT number

2022-502790-42-00

ClinicalTrials.gov

NCT05583071

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

to estimate the efficacy of the Methotrexate, Tafasitamab, Rituximab, Revlimid (MTR²) regimen, to develop a feasible and effective regimen for the treatment of PCNSL patients who are unable to receive intensice induction and consolidation therapies.

Secondary objectives 5

1. To describe the safety during therapy with 4 cycles MTR2
2. To describe the feasibility of 4 cycles MTR2
3. To describe the efficacy of 4 cycles MTR2 in terms of BOR, PFS and OS rate at 1 years
4. To describe the quality of life over time
5. To describe neurocognitive impairment over time

Conditions and MedDRA coding

Primary Central Nervous Lymphoma (PCNSL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age 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: o Adequate kidney function, defined as:  Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 60 ml/min o Adequate hepatic function, defined as:  ALAT and ASAT ≤ 3 ULN  Bilirubin ≤ 2.0 mg/dl (except for Meulengracht disease) o 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 o Adequate cardiac function, defined as:  Cardiac ejection fraction ≥ 40% o 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 as described in Section12.1.2.1
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 15

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: a. Surgically cured carcinoma in-situ b. 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: a. Increased alcohol consumption, Ddrug dependency or substance abuse that would interfere with cooperation with requirements of the trial b. Refusal of blood products during treatment c. Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible
15. Relationship of dependence or employeremployee relationship to the sponsor or the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy will be determined using the complete response rate (CRR) after at least 2 cycles of treatment with MTR² (Methotrexate, Tafasitamab, Rituximab, Revlimid), as determined by independent review committee (IRC) and according to International Primary CNS Lymphoma Collaborative Group (IPCG) criteria

Secondary endpoints 8

1. Best overall response rate (BORR) after 4 cycles of MTR² is defined as the rate of patients having achieved a CR or PR according to at least one post-baseline tumor assessment
2. Objective response rate (ORR) at RA I and RA II defined as rate of patients showing CR, CRr or PR
3. 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 . One-year PFS rates and 90% confidence intervals will be estimated using the Kaplan-Meier method.
4. 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 followup (FU-eCRF, QoL CRF or written medical report). One-year OS rates and 90% confidence intervals will be estimated using the Kaplan-Meier method.
5. Incidence and severity of adverse events, including toxic deaths during induction therapy will be summarized based on CTCAE grades
6. Quality of life and neurocognitive impairment over time as determined by EORTC QLQC30 and BN20 questionnaires as well as Montreal Cognitive Assessment (MoCA), respectively
7. Safety as determined by incidence and severity of adverse events
8. Feasibility as determined by proportion of patients completing 4 cycles of MTR2 and relative dose intensity of planned and administered cycles

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Cologne

Sponsor organisation

University Of Cologne

Address

Albertus-Magnus-Platz 1

City

Cologne

Postcode

50923

Country

Germany

Scientific contact point

Organisation

University Of Cologne

Contact name

Peter Borchmann

Public contact point

Organisation

University Of Cologne

Contact name

Peter Borchmann

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications