OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma (OptiMATe)

March 16, 2026 updated by: Klinikum Stuttgart

Optimizing MATRix as Remission Induction in PCNSL: De-escalated Induction Treatment in Newly Diagnosed Primary CNS Lymphoma - a Randomized Phase III Trial

This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival. Two arms are compared, in the experimental treatment group, participants receive one course of R/HD-MTX, followed by two courses of MATRix and autologous stem cell transplantation. In the control treatment, participants receive four coourses of MATRix followed by autologous stem cell transplantation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
331

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
    • Baden-Wurttemberg
      • Stuttgart, Baden-Wurttemberg, Germany, 70174
        • Klinikum Stuttgart

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
  2. Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
  3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy.
  4. Disease exclusively located in the CNS.
  5. At least one measurable lesion.
  6. Previously untreated patients (previous or ongoing steroid treatment admitted)
  7. Negative pregnancy test
  8. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
  9. Ability to understand the nature of the trial and the trial related procedures and to comply with them.

Exclusion Criteria:

  1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
  2. Systemic lymphoma manifestation (outside the CNS).
  3. Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
  4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years.
  5. Previous Non-Hodgkin lymphoma at any time.
  6. Inadequate renal function (clearance < 60 ml/min).
  7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
  8. Active hepatitis B or C disease.
  9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study.
  10. Third space fluid accumulation > 500 ml.
  11. Hypersensitivity to study treatment or any component of the formulation.
  12. Taking any medications that are likely to cause interactions with the study medication
  13. Known or persistent abuse of medication, drugs or alcohol.
  14. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
  15. Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
  16. Previous participation in this trial.
  17. Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
  18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  19. Current or planned pregnancy, nursing period
  20. For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Control treatment (Arm A)
Patients receive four courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) as induction treatment. Response assessment with gadolinium-enhanced brain MRI (centrally reviewed) takes place after course two and four. Patient with at least PR proceed to 3rd course of MATRix after first response assessment and to HCT-ASCT (BCNU 400 mg/m2, Thiotepa 4 x 5 mg/kg; i.v.) after second response assessment. Collection of autologous stem cells is planed after the second course of MATRix.
Drug: Control intervention: four courses of MATRix
Patients receive four courses of MATRix as induction treatment.
Experimental: Experimental treatment (Arm B)
As induction treatment, patients receive one course of Rituximab/HD-Methotrexate (Rituximab 375 mg/m2, HD-Methotrexate 3.5 g/m2; i.v.). In the absence of clinical signs of progression, patients proceed to two courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) followed by a response assessment with gadolinium-enhanced brain MRI (centrally reviewed). Patients with at least PR will proceed to HCT-ASCT (BCNU 400 mg/m2, thiotepa 4 x 5 mg/kg; i.v.). Collection of autologous stem cells is planed after the first course of MATRix
Drug: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix
De-escalated induction treatment with R/HD-MTX and two courses of MATRix

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: up to 24 months after end of treatment
time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first
up to 24 months after end of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: up to 24 months after end of treatment
time from randomization to death of any course
up to 24 months after end of treatment
Progression free survival (PFS)
Time Frame: up to 24 months after end of treatment
time from randomization until disease progression, relapse or death from any cause
up to 24 months after end of treatment
Remission rate prior to consolidation therapy
Time Frame: assesed at RA II (Arm B: day 18-20 of cycle 2, each cycle is 21 days. Arm A: day 18-20 of cycle 4, each cycle is 21 days)
Remission prior to consolidation therapy will be determined at RA II and will be divided in CR, uCR, PR, CD, PD according to IPCG criteria
assesed at RA II (Arm B: day 18-20 of cycle 2, each cycle is 21 days. Arm A: day 18-20 of cycle 4, each cycle is 21 days)
Remission rate after consolidation therapy
Time Frame: 30 days after ASCT
Remission after consolidation therapy will be determined on day 30 after ASCT and will be divided in CR, uCR, PR, SD, PD according to IPCG criteria
30 days after ASCT
rate of patients reaching consolidation therapy
Time Frame: determined up to 4 weeks after response assessment II
defined as obtaining at least the first dose of consolidation therapy, will be determined after the response assessment II (following 4 cycles of MATRix in the control arm and following 1 cycle of R/HD-MTX and 2 cycles of MATRix in the experimental arm)
determined up to 4 weeks after response assessment II
Quality of life (QOL), EORTC QLQ-C30,
Time Frame: up to 24 months after end of treatment
EORTC (European Organization for research and cancer treatment) QLQ-C30, measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up
up to 24 months after end of treatment
Quality of life (QOL), QLQ-BN20
Time Frame: up to 24 months after end of treatment
EORTC (European Organization for research and cancer treatment) QLQ-BN20; measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up
up to 24 months after end of treatment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison of de-escalated regimen to standard induction therapy regarding safety
Time Frame: up to 60 days after ASCT
incidence of (Serious) adverse events, laboratory parameters:WBC <2.500/µl and platelets <80.000/μl , vital signs: blood pressure (mmHg), heart rate (bpm)
up to 60 days after ASCT
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
MoCA (Montreal Cognitive Assesment) performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
WAIS III (Wechsler Adult Intelligence scale) counting test performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
WAIS III (Wechsler Adult Intelligence scale) subtest similarities and verbal fluency test performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
Trail Making Test A and B, performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
Brief Test of Attention performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
Hopkins Verbal Learning Test performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
Grooved Pegboard Test, performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Time Frame: up to 24 months after end of treatment
Rey-Osterrieth-Complex-Figure-Test performed at screening, EOT and every 12 months until end of follow-up
up to 24 months after end of treatment
Unplanned hospital admissions
Time Frame: up to 6 months after EOT visit
Defined as in-patient hospitalization from randomization until 6 months after EOT visit (excluding those for study therapy and/or assessments, placement of an indwelling catheter, social/convenience admissions, respite care, elective or pre-planned treatment/surgery)
up to 6 months after EOT visit
Length of hospital stays
Time Frame: up to 6 months after EOT visit
Measured as number of nights in hospital from randomization and until 6 months after EOT. Hospitalization must be in relation to the disease or the administered treatment or due to toxicity
up to 6 months after EOT visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Klinikum Stuttgart

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
German Federal Ministry of Education and Research
University Hospital Freiburg

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gerald Illerhaus, Prof, Klinikum Stuttgart

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 28, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 25, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SCC215

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After approval through ethics committee publication of study protocol. Anonymised patient data can be provided upon project related request.

IPD Sharing Time Frame

Study protocol: 1st quarter 2021 Not before 2nd quarter 2028: Anonymised patient data

IPD Sharing Access Criteria

To get access to anonymised patient data, a research proposal/project plan is required.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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