NCT06830421

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

Age-adjusted High-dose Chemotherapy Followed by Autologous Stem Cell Transplantation or Conventional Chemotherapy With R-MP as First-line Treatment in Elderly Primary CNS Lymphoma Patients - a Randomized Phase III Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 340 (estimated)
• Sponsor: University Hospital Freiburg · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. However, there are alternative treatment approaches to consider with the potential to improve medical outcomes for this patient population. The current standard of care in Germany and many international centres for patients 65 and older is treatment with R-MP, comprising rituximab, high-dose methotrexate (HD-MTX) and procarbazine followed by maintenance therapy with procarbazine. An alternative approach comprised of a shorter induction treatment with rituximab, HD-MTX and cytarabine (MARTA) followed by age-adjusted high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) was recently shown to be feasible and effective in elderly PCNSL patients considered eligible for high-dose chemotherapy requiring autologous stem cell transplantation. Nevertheless, data evaluating this short duration treatment approach remains scarce, and randomized trials have not yet been published. The objective of the PRIMA-CNS trial is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with R-MP followed by maintenance with procarbazine in elderly patients with newly diagnosed PCNSL; not only regarding survival and remission after treatment but also regarding standards like quality of life (QOL) and treatment related morbidities. Results of this randomized trial will either change the standard of care to an intense and shorter treatment approach or re-define R-MP as a proven treatment standard. In addition, a geriatric assessement is implemented in this trial with the goal to better define transplant eligibility. If this trial shows the superiority of HCT-ASCT, the investigators will establish an improved treatment standard with increased chances for long-term remission and cure and reduced frequency and length of chemotherapy treatment. Considering the poor prognosis of this patient population, this randomized phase III trial is of great clinical importance to provide patients, the patients' families and care takers with optimal treatment.

Conditions

• Primary Central Nervous System Lymphoma

Interventions

Type	Name	Description
DRUG	R-MP and Procarbazine maintenance	Firstline systemic treatment with conventinal immunochemotherapy (3 cycles of Rituximab-MTX-Procarbazine) followed by Procarbazine maintenance
DRUG	R-MTX/AraC (MARTA) induction followed by consolidating HCT-ASCT	Firstline systemic treatment with age-adjusted MTX based induction (2 cycles of Rituximab-Methotrexate-Cytarabin) followed by consolidating aged-adapted high-dose chemotherapy and autologous stem cell transplantation

Timeline

• Start date: 2023-08-09
• Primary completion: 2029-08-31
• Completion: 2031-08-31
• First posted: 2025-02-17
• Last updated: 2025-02-17

Locations

35 sites across 1 country: Germany