High-dose chemotherapy with stem cell transplant versus standard treatment for elderly patients with brain lymphoma

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

This study is testing whether a stronger chemotherapy treatment with stem cell transplant can help older patients with brain lymphoma live longer and feel better compared to the usual treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 340 (estimated)
• Ages: 65 Years and up
• Sex: All
• Sponsor: University Hospital Freiburg (Academic / other)
• Drugs / interventions: Rituximab, chemotherapy, methotrexate
• Locations: 35 sites (Freiburg im Breisgau, Baden-Wurttemberg and 34 other locations)
• Trial ID: NCT06830421 on ClinicalTrials.gov

What this trial studies

This clinical trial compares two treatment approaches for elderly patients diagnosed with primary central nervous system lymphoma (PCNSL). One group will receive the conventional R-MP regimen, which includes rituximab, high-dose methotrexate, and procarbazine, followed by maintenance therapy. The other group will undergo a shorter induction treatment with rituximab, high-dose methotrexate, and cytarabine, followed by high-dose chemotherapy and autologous stem cell transplantation. The goal is to determine if the intensified chemotherapy approach leads to better survival rates and quality of life compared to the standard treatment.

Who should consider this trial

Good fit: Ideal candidates are immunocompetent patients aged 65 years or older with newly diagnosed primary DLBCL of the central nervous system.

Not a fit: Patients with PCNSL who are not eligible for high-dose chemotherapy or have performance status greater than 2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly improve survival and quality of life for elderly patients with PCNSL.

How similar studies have performed: While similar treatment approaches have shown promise, this specific comparison of intensified chemotherapy versus standard treatment in elderly PCNSL patients is novel and has not been previously published.

Eligibility criteria

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.

Where this trial is running

Freiburg im Breisgau, Baden-Wurttemberg and 34 other locations

• University Hospital Freiburg, Department Medicine I, Hematology, oncology and stem cell transplantation — Freiburg im Breisgau, Baden-Wurttemberg, Germany (Recruiting)
• Klinikum Stuttgart, Clinic of Hematology, Oncology and Palliative Care, Stuttgart Cancer Center / Tumor Center Eva Mayr-Stihl — Stuttgart, Baden-Wurttemberg, Germany (Recruiting)
• University Hospital Aachen — Aachen, Germany (Recruiting)
• University Hospital Augsburg — Augsburg, Germany (Recruiting)
• Helios Klinikum Berlin-Buch — Berlin, Germany (Not_yet_recruiting)
• University Hospital Berlin — Berlin, Germany (Recruiting)
• Evangelisches Klinikum Bethel — Bielefeld, Germany (Not_yet_recruiting)
• Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH — Bochum, Germany (Recruiting)
• Städtisches Klinikum Braunschweig gGmbH — Braunschweig, Germany (Recruiting)
• Klinikum Bremen-Mitte gGmbH — Bremen, Germany (Recruiting)
• Klinikum Chemnitz gGmbH — Chemnitz, Germany (Not_yet_recruiting)
• Universitätsklinikum Köln — Cologne, Germany (Not_yet_recruiting)
• Carl Gustav Carus Universitätsklinikum Dresden — Dresden, Germany (Recruiting)
• Universitätsklinikum Düsseldorf — Düsseldorf, Germany (Not_yet_recruiting)
• Universitätsklinikum Erlangen — Erlangen, Germany (Recruiting)
• Universitätsklinikum Essen — Essen, Germany (Not_yet_recruiting)
• Klinikum der Johann-Wolfgang-Goethe-Universität — Frankfurt, Germany (Recruiting)
• Universitätsmedizin Göttingen Georg-August-Universität — Göttingen, Germany (Not_yet_recruiting)
• Universitätsklinikum Halle (Saale) — Halle, Germany (Not_yet_recruiting)
• Universitätsklinikum des Saarlandes Homburg — Homburg, Germany (Recruiting)
• Städtisches Klinikum Karlsruhe — Karlsruhe, Germany (Recruiting)
• Universitätsklinkum Schleswig-Holstein, Campus Kiel — Kiel, Germany (Recruiting)
• Gemeinschaftsklinikum Mittelrhein gGmbH - Koblenz Ev. Stift St. Martin — Koblenz, Germany (Recruiting)
• Universitätsklinikum Leipzig — Leipzig, Germany (Not_yet_recruiting)
• Universitätsklinikum Schleswig-Holstein, Campus Lübeck — Lübeck, Germany (Recruiting)
• Klinikum rechts der Isar TU München — München, Germany (Not_yet_recruiting)
• Universitätsklinikum Münster — Münster, Germany (Recruiting)
• Universitätsklinik der Paracelsus Medizinischen Privatuniversität — Nuremberg, Germany (Not_yet_recruiting)
• Pius-Hospital Oldenburg — Oldenburg, Germany (Recruiting)
• Klinikum Oldenburg gGmbh — Oldenburg in Holstein, Germany (Not_yet_recruiting)
• Universitätsklinikum Regensburg — Regensburg, Germany (Recruiting)
• Universitätsmedizin Rostock — Rostock, Germany (Not_yet_recruiting)
• Universtitätsklinikum Tübingen — Tübingen, Germany (Not_yet_recruiting)
• Universitätsklinikum Ulm — Ulm, Germany (Recruiting)
• Schwarzwald-Baar-Klinikum Villingen-Schwenningen — Villingen-Schwenningen, Germany (Recruiting)

Study contacts

• Study coordinator: Elisabeth Schorb, MD

Conditions Primary Central Nervous System Lymphoma; Primary central nervous system lymphoma; HD-chemotherapy followed by autologous stem cell transplantation; Age-adjusted HCT-ASCT; First-line treatment in elderly PCNSL patients; HD-MTX induction