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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 65 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06830421
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University Hospital Freiburg
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Germany
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Primary Central Nervous System Lymphoma
Additional Details

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.

Arms & Interventions

Arms

Active Comparator: Arm A

Patients will receive 3 cycles (28 days cycle) of R-MP (Rituximab 375 mg/m² i.v. d0,14; MTX 3.5 g/m² i.v. d1,15; Procarbazine 60 mg/m²/d p.o. d2-11) followed by maintenance therapy with Procarbazine 100 mg absolute/d p.o. d1-5 for additional 6 cycles (28 days cycle).

Experimental: Arm B

Patients will receive 2 cycles (21 days cycle) of R-MTX/AraC (Rituximab 375 mg/m² i.v. d0,4; MTX 3.5 g/m² i.v. d1; AraC 2x2 g/m² i.v. d2+d3) followed by consolidating HCT-ASCT with Rituximab 375 mg/m² d-8, Busulfan 3.2 mg/kg/d i.v. d-7 and d-6 and Thiotepa 5 mg/kg/d i.v. d-5 and d-4.

Interventions

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Freiburg, Baden-Wuerttemberg, Germany

Status

Recruiting

Address

University Hospital Freiburg, Department Medicine I, Hematology, oncology and stem cell transplantation

Freiburg, Baden-Wuerttemberg, 79106

Site Contact

Elisabeth Schorb, MD

[email protected]

+4976127035360

Stuttgart, Baden-Wuerttemberg, Germany

Status

Recruiting

Address

Klinikum Stuttgart, Clinic of Hematology, Oncology and Palliative Care, Stuttgart Cancer Center / Tumor Center Eva Mayr-Stihl

Stuttgart, Baden-Wuerttemberg, 70174

Site Contact

Gerald Illerhaus, PhD

[email protected]

+49 711 278 #30400

University Hospital Aachen, Aachen, Germany

Status

Recruiting

Address

University Hospital Aachen

Aachen, ,

Site Contact

Jens Panse, MD

[email protected]

+49 761 270-35360

University Hospital Augsburg, Augsburg, Germany

Status

Recruiting

Address

University Hospital Augsburg

Augsburg, ,

Site Contact

Mathias Lutz, MD

[email protected]

+49 761 270-35360

Helios Klinikum Berlin-Buch, Berlin, Germany

Status

Not yet recruiting

Address

Helios Klinikum Berlin-Buch

Berlin, ,

Site Contact

Christian Eimermacher, MD

[email protected]

+49 761 270-35360

University Hospital Berlin, Berlin, Germany

Status

Recruiting

Address

University Hospital Berlin

Berlin, ,

Site Contact

Ulrich Keller, MD

[email protected]

+49 761 270-35360

Evangelisches Klinikum Bethel, Bielefeld, Germany

Status

Not yet recruiting

Address

Evangelisches Klinikum Bethel

Bielefeld, ,

Site Contact

Bettina Zinngrebe, MD

[email protected]

+49 761 270-35360

Bochum, Germany

Status

Recruiting

Address

Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH

Bochum, ,

Site Contact

Sabine Seidel, MD

[email protected]

+49 761 270-35360

Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany

Status

Recruiting

Address

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, ,

Site Contact

Carsten Springer, MD

[email protected]

+49 761 270-35360

Klinikum Bremen-Mitte gGmbH, Bremen, Germany

Status

Recruiting

Address

Klinikum Bremen-Mitte gGmbH

Bremen, ,

Site Contact

Bernd Hertenstein, MD

[email protected]

+49 761 270-35360

Klinikum Chemnitz gGmbH, Chemnitz, Germany

Status

Not yet recruiting

Address

Klinikum Chemnitz gGmbH

Chemnitz, ,

Site Contact

Mathias Hänel, MD

[email protected]

+49 761 270-35360

Dresden, Germany

Status

Recruiting

Address

Carl Gustav Carus Universitätsklinikum Dresden

Dresden, ,

Site Contact

Frank Kroschinsky, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Düsseldorf, Düsseldorf, Germany

Status

Not yet recruiting

Address

Universitätsklinikum Düsseldorf

Düsseldorf, ,

Site Contact

Guido Kobbe, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Erlangen, Erlangen, Germany

Status

Recruiting

Address

Universitätsklinikum Erlangen

Erlangen, ,

Site Contact

Stefan Krause, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Essen, Essen, Germany

Status

Not yet recruiting

Address

Universitätsklinikum Essen

Essen, ,

Site Contact

Bastian von Tresckow, MD

[email protected]

+49 761 270-35360

Frankfurt, Germany

Status

Recruiting

Address

Klinikum der Johann-Wolfgang-Goethe-Universität

Frankfurt, ,

Site Contact

Thomas Oellerich, MD

[email protected]

+49 761 270-35360

Göttingen, Germany

Status

Not yet recruiting

Address

Universitätsmedizin Göttingen Georg-August-Universität

Göttingen, ,

Site Contact

Justin Hasenkamp, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Halle (Saale), Halle (Saale), Germany

Status

Not yet recruiting

Address

Universitätsklinikum Halle (Saale)

Halle (Saale), ,

Site Contact

Thomas Weber, MD

[email protected]

+49 761 270-35360

Homburg, Germany

Status

Recruiting

Address

Universitätsklinikum des Saarlandes Homburg

Homburg, ,

Site Contact

Lorenz Thurner, MD

[email protected]

+49 761 270-35360

Städtisches Klinikum Karlsruhe, Karlsruhe, Germany

Status

Recruiting

Address

Städtisches Klinikum Karlsruhe

Karlsruhe, ,

Site Contact

Martin Bentz, MD

[email protected]

+49 761 270-35360

Kiel, Germany

Status

Recruiting

Address

Universitätsklinkum Schleswig-Holstein, Campus Kiel

Kiel, ,

Site Contact

Christine Pott, MD

[email protected]

+49 761 270-35360

Koblenz, Germany

Status

Recruiting

Address

Gemeinschaftsklinikum Mittelrhein gGmbH - Koblenz Ev. Stift St. Martin

Koblenz, ,

Site Contact

Niemann Dirk, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Köln, Köln, Germany

Status

Not yet recruiting

Address

Universitätsklinikum Köln

Köln, ,

Site Contact

Heger Jan-Michel, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Leipzig, Leipzig, Germany

Status

Not yet recruiting

Address

Universitätsklinikum Leipzig

Leipzig, ,

Site Contact

Simone Heyn, MD

[email protected]

+49 761 270-35360

Luebeck, Germany

Status

Recruiting

Address

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Luebeck, ,

Site Contact

Nicolas von Bubnoff, MD

[email protected]

+49 761 270-35360

Klinikum rechts der Isar TU München, München, Germany

Status

Not yet recruiting

Address

Klinikum rechts der Isar TU München

München, ,

Site Contact

Lena Illert, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Münster, Münster, Germany

Status

Recruiting

Address

Universitätsklinikum Münster

Münster, ,

Site Contact

Andrea Kerkhoff, MD

[email protected]

+49 761 270-35360

Nürnberg, Germany

Status

Not yet recruiting

Address

Universitätsklinik der Paracelsus Medizinischen Privatuniversität

Nürnberg, ,

Site Contact

Alexander Bott, MD

[email protected]

+49 761 270-35360

Klinikum Oldenburg gGmbh, Oldenburg In Holstein, Germany

Status

Not yet recruiting

Address

Klinikum Oldenburg gGmbh

Oldenburg In Holstein, ,

Site Contact

Christoph Kimmich, MD

[email protected]

+49 761 270-35360

Pius-Hospital Oldenburg, Oldenburg, Germany

Status

Recruiting

Address

Pius-Hospital Oldenburg

Oldenburg, ,

Site Contact

Johannes Hoffmann, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Regensburg, Regensburg, Germany

Status

Recruiting

Address

Universitätsklinikum Regensburg

Regensburg, ,

Site Contact

Florian Lüle, MD

[email protected]

+49 761 270-35360

Universitätsmedizin Rostock, Rostock, Germany

Status

Not yet recruiting

Address

Universitätsmedizin Rostock

Rostock, ,

Site Contact

Christoph Wittke, MD

[email protected]

+49 761 270-35360

Universtitätsklinikum Tübingen, Tübingen, Germany

Status

Not yet recruiting

Address

Universtitätsklinikum Tübingen

Tübingen, ,

Site Contact

Robert Möhle, MD

[email protected]

+49 761 270-35360

Universitätsklinikum Ulm, Ulm, Germany

Status

Recruiting

Address

Universitätsklinikum Ulm

Ulm, ,

Site Contact

Andreas Viardot, MD

[email protected]

+49 761 270-35360

Villingen-Schwenningen, Germany

Status

Recruiting

Address

Schwarzwald-Baar-Klinikum Villingen-Schwenningen

Villingen-Schwenningen, ,

Site Contact

Paul La Rosée, MD

[email protected]

+49 761 270-35360

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