De-escalated treatment for primary CNS lymphoma

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

This study is testing a new, less intense treatment for people with newly diagnosed primary CNS lymphoma to see if it can help them live longer without cancer events compared to the standard treatment.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 326 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Klinikum Stuttgart (other)
• Locations: 1 site (Stuttgart, Baden-Württemberg)
• Trial ID: NCT04931368 on ClinicalTrials.gov

What this trial studies

This phase III study compares a de-escalated induction treatment for newly diagnosed primary CNS lymphoma against the standard MATRix protocol to determine which approach leads to better event-free survival. Participants in the experimental group will receive one course of Rituximab/HD-Methotrexate followed by two courses of MATRix and autologous stem cell transplantation. In contrast, the control group will undergo four courses of MATRix followed by the same stem cell transplantation. The study aims to identify a potentially less intensive treatment regimen that maintains efficacy while reducing treatment burden.

Who should consider this trial

Good fit: Ideal candidates are immunocompetent adults aged 18-70 with newly diagnosed primary diffuse large B-cell lymphoma located exclusively in the CNS.

Not a fit: Patients with previously treated CNS lymphoma or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a less intensive treatment option for patients with primary CNS lymphoma, potentially improving their quality of life and treatment outcomes.

How similar studies have performed: Other studies have explored de-escalated treatment approaches in various cancers, showing promising results, but this specific approach in primary CNS lymphoma is novel.

Eligibility criteria

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.

Where this trial is running

Stuttgart, Baden-Württemberg

• Klinikum Stuttgart — Stuttgart, Baden-Württemberg, Germany (RECRUITING)

Study contacts

• Principal investigator: Gerald Illerhaus, Prof — Klinikum Stuttgart
• Study coordinator: Gerald Illerhaus, Prof

Conditions: Primary Central Nervous System Lymphoma