Primary Central Nervous System LymphomaPhase 3OptiMATeNCT04931368
OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma
A Phase 3 study testing Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix in people with Primary Central Nervous System Lymphoma, run by Klinikum Stuttgart at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Primary Central Nervous System Lymphoma
- What is being tested?
- Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 331 participants
- Where
- 1 siteGermany
- Study dates
- 28 Jun 2021to Nov 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
- Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
- 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.
- Disease exclusively located in the CNS.
- At least one measurable lesion.
- Previously untreated patients (previous or ongoing steroid treatment admitted)
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- Negative pregnancy test
- 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.
- Ability to understand the nature of the trial and the trial related procedures and to comply with them.
Who cannot join
- Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
- Systemic lymphoma manifestation (outside the CNS).
- Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
- 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.
- Previous Non-Hodgkin lymphoma at any time.
- Inadequate renal function (clearance < 60 ml/min).
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- Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
- Active hepatitis B or C disease.
- 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.
- Third space fluid accumulation > 500 ml.
- Hypersensitivity to study treatment or any component of the formulation.
- Taking any medications that are likely to cause interactions with the study medication
- Known or persistent abuse of medication, drugs or alcohol.
- Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
- Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
- Previous participation in this trial.
- Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
- Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Current or planned pregnancy, nursing period
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Primary Central Nervous System Lymphoma
- Being tested
- Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix, Control intervention: four courses of MATRix
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRixDrug
De-escalated induction treatment with R/HD-MTX and two courses of MATRix
Control intervention: four courses of MATRixDrug
Patients receive four courses of MATRix as induction treatment.
| Study group | Role | What they receive |
|---|---|---|
| Control treatment (Arm A) | Active comparator | 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. Receives: Drug: Control intervention: four courses of MATRix |
| Experimental treatment (Arm B) | Experimental | 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 Receives: Drug: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first
Measured: up to 24 months after end of treatment
Secondary outcomes (7)
Overall survival (OS)
time from randomization to death of any course
Measured: up to 24 months after end of treatment
Progression free survival (PFS)
time from randomization until disease progression, relapse or death from any cause
Measured: up to 24 months after end of treatment
Remission rate prior to consolidation therapy
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
Measured: 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
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
Measured: 30 days after ASCT
rate of patients reaching consolidation therapy
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)
Measured: determined up to 4 weeks after response assessment II
Quality of life (QOL), EORTC QLQ-C30,
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
Measured: up to 24 months after end of treatment
Quality of life (QOL), QLQ-BN20
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
Measured: up to 24 months after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start28 Jun 2021
- Primary completionJun 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 331 participants (actual)
Sponsor and investigators
- Lead sponsor
- Klinikum Stuttgart
- Sponsor type
- University, hospital or other
- Collaborators
- German Federal Ministry of Education and Research, University Hospital Freiburg
- Responsible party
- Sponsor
- Investigators
- Gerald Illerhaus, Prof, Principal investigator, Klinikum Stuttgart
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04931368
- Sponsor's protocol ID
- SCC215
- Acronym
- OptiMATe
- Status last verified
- Apr 2025
- First submitted
- 25 Aug 2020
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After approval through ethics committee publication of study protocol. Anonymised patient data can be provided upon project related request.
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing MATRix as Remission Induction in PCNSL: De-escalated Induction Treatment in Newly Diagnosed Primary CNS Lymphoma - a Randomized Phase III Trial
- ClinicalTrials.gov ID
- NCT04931368
- Acronym / sponsor ID
- OptiMATe / SCC215
- Conditions
- Primary Central Nervous System Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 331 participants (actual)
- Lead sponsor
- Klinikum StuttgartUniversity, hospital or other
- Collaborators
- German Federal Ministry of Education and Research, University Hospital Freiburg
- Study start
- 28 Jun 2021 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 18 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control treatment (Arm A) | Active comparator | Drug: Control intervention: four courses of MATRixPatients 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. |
| Experimental treatment (Arm B) | Experimental | Drug: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRixAs 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
- Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
- 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.
- Disease exclusively located in the CNS.
- At least one measurable lesion.
Key exclusion criteria (20 listed)
- Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
- Systemic lymphoma manifestation (outside the CNS).
- Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
- 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.
- Previous Non-Hodgkin lymphoma at any time.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRixDe-escalated induction treatment with R/HD-MTX and two courses of MATRix | Drug | Experimental treatment (Arm B) |
| Control intervention: four courses of MATRixPatients receive four courses of MATRix as induction treatment. | Drug | Control treatment (Arm A) |
Primary outcome
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
7 secondary outcomes
Overall survival (OS)
Time frame: up to 24 months after end of treatment
Progression free survival (PFS)
Time frame: 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 rate after consolidation therapy
Time frame: 30 days after ASCT
rate of patients reaching consolidation therapy
Time frame: 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
Quality of life (QOL), QLQ-BN20
Time frame: up to 24 months after end of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Individual participant dataSharing planned: Yes. After approval through ethics committee publication of study protocol. Anonymised patient data can be provided upon project related request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerald Illerhaus, Prof principal investigator
Klinikum Stuttgart
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix in people with Primary Central Nervous System Lymphoma, run by Klinikum Stuttgart at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (EFS) (time frame: up to 24 months after end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.