Adjusted High-dose Chemotherapy With Autologous Stem Cell Transplant vs. Conventional Immunochemotherapy in Elderly PCNSL Patients

Most patients being diagnosed with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) are 60 years or older. Elderly patients with PCNSL have a poor prognosis and there is a great medical need to improve outcome for this vulnerable population. In Germany and many international centres, there are currently two widely used strategies to treat elderly PCNSL patients who are eligible for high-dose methotrexate (HD-MTX) treatment, which have not yet been compared head-to-head. The R-MP regimen has been established by the Cooperative PCNSL Study Group as a "conventional" immunochemotherapy standard treatment for elderly patients with newly diagnosed disease and consists of Rituximab, HD-MTX and Procarbazine followed by maintenance therapy with Procarbazine. In contrast, another recently established protocol also includes HD-MTX-based induction therapy, but followed by consolidating high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT). This is an overall more intensive, but substantially shorter treatment approach, feasible for elderly patients being considered eligible for a more intensive treatment. The PRIMA-CNS trial aims to compare these two treatment approaches with respect to survival, response rates and toxicity.

Sex

All

Minimum age

65 Years

Inclusion Criteria:

1. Immunocompetent patients with newly-diagnosed primary DLBCL of the central nervous system.
2. Age \> 70 years or age 65-70 years if not eligible for more intensive treatment (e.g. OptiMATe trial).
3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist.
4. Diagnostic sample obtained by stereotactic or surgical biopsy, cerebrospinal fluid (CSF) cytology examination or vitrectomy.
5. Disease exclusively located in the CNS.
6. At least 1 measurable lesion.
7. Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) ≤ 2. ECOG PS \> 2 accepted if due to PCNSL symptoms.
8. Patients possibly eligible for HCT-ASCT as judged by the treating physician.
9. 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.

Additional randomization criteria:

1. Patients eligible for HCT-ASCT defined by the EBL score (at most one of the 3 following conditions may apply: ECOG PS \> 1, Barthel Index of activities of daily living (ADL) \< 20 and Lachs geriatric screening \> 3), improvement of PS after pre-phase treatment or clinical judgement by the treating physician after discussion with the study expert team.
2. No evidence of disease progression after pre-phase treatment.

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 or primary leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord.
4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ or other kinds of cancer without evidence of disease for at least 5 years.
5. Previous systemic Non-Hodgkin lymphoma at any time.
6. Inadequate renal function (creatinine 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 administration of study medication within the last thirty 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 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 and who are unable to understand the nature, significance and consequences of the study and without designated legal representative.
16. Previous participation in this trial.
17. Persons who are in a relationship of dependency/employment to the sponsor and/ or investigator.
18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
19. Fertile patients refusing to use safe contraceptive methods during the study.

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