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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Central Nervous System Lymphoma
• Intervention / Treatment: Drug: R-MP and Procarbazine maintenance; Drug: R-MTX/AraC (MARTA) induction followed by consolidating HCT-ASCT

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.

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Elisabeth Schorb, MD; Phone Number: +49 761 270-35360; Email: elisabeth.schorb@uniklinik-freiburg.de
• Study Contact Backup: Name: Gerald Illerhaus, MD; Phone Number: +49 711 278-30400; Email: g.illerhaus@klinikum-stuttgart.de

Study Locations

• Germany
  • Aachen, Germany
    • Recruiting
    • University Hospital Aachen
    • Contact: Jens Panse, MD; Email: jpanse@ukaachen.de
  • Augsburg, Germany
    • Recruiting
    • University Hospital Augsburg
    • Contact: Mathias Lutz, MD; Email: mathias.lutz@uk-augsburg.de
  • Berlin, Germany
    • Recruiting
    • University Hospital Berlin
    • Contact: Ulrich Keller, MD; Email: ulrich.keller@charite.de
  • Berlin, Germany
    • Not yet recruiting
    • Helios Klinikum Berlin-Buch
    • Contact: Christian Eimermacher, MD; Email: Christian.eimermacher@helios-gesundheit.de
  • Bielefeld, Germany
    • Not yet recruiting
    • Evangelisches Klinikum Bethel
    • Contact: Bettina Zinngrebe, MD; Email: bettina.zinngrebe@evkb.de
  • Bochum, Germany
    • Recruiting
    • Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH
    • Contact: Sabine Seidel, MD; Email: Sabine.Seidel@kk-bochum.de
  • Braunschweig, Germany
    • Recruiting
    • Städtisches Klinikum Braunschweig gGmbH
    • Contact: Carsten Springer, MD; Email: c.springer@klinikum-braunschweig.de
  • Bremen, Germany
    • Recruiting
    • Klinikum Bremen-Mitte gGmbH
    • Contact: Bernd Hertenstein, MD; Email: bernd.hertenstein@klinikum-bremen-mitte.de
  • Chemnitz, Germany
    • Not yet recruiting
    • Klinikum Chemnitz gGmbH
    • Contact: Mathias Hänel, MD; Email: m.haenel@skc.de
  • Dresden, Germany
    • Recruiting
    • Carl Gustav Carus Universitätsklinikum Dresden
    • Contact: Frank Kroschinsky, MD; Email: frank.kroschinsky@uniklinikum-dresden.de
  • Düsseldorf, Germany
    • Not yet recruiting
    • Universitätsklinikum Düsseldorf
    • Contact: Guido Kobbe, MD; Email: kobbe@med.uni-duesseldorf.de
  • Erlangen, Germany
    • Recruiting
    • Universitätsklinikum Erlangen
    • Contact: Stefan Krause, MD; Email: stefan.krause@uk-erlangen.de
  • Essen, Germany
    • Not yet recruiting
    • Universitatsklinikum Essen
    • Contact: Bastian von Tresckow, MD; Email: bastian.vontresckow@uk-essen.de
  • Frankfurt, Germany
    • Recruiting
    • Klinikum der Johann-Wolfgang-Goethe-Universität
    • Contact: Thomas Oellerich, MD; Email: thomas.oellerich@kgu.de
  • Göttingen, Germany
    • Not yet recruiting
    • Universitätsmedizin Göttingen Georg-August-Universität
    • Contact: Justin Hasenkamp, MD; Email: j.hasenkamp@med.uni-goettingen.de
  • Halle (Saale), Germany
    • Not yet recruiting
    • Universitätsklinikum Halle (Saale)
    • Contact: Thomas Weber, MD; Email: thomas.weber@uk-halle.de
  • Homburg, Germany
    • Recruiting
    • Universitätsklinikum des Saarlandes Homburg
    • Contact: Lorenz Thurner, MD; Email: lorenz.thurner@uks.eu
  • Karlsruhe, Germany
    • Recruiting
    • Stadtisches Klinikum Karlsruhe
    • Contact: Martin Bentz, MD; Email: martin.bentz@klinikum-karlsruhe.de
  • Kiel, Germany
    • Recruiting
    • Universitätsklinkum Schleswig-Holstein, Campus Kiel
    • Contact: Christine Pott, MD; Email: c.pott@med2.uni-kiel.de
  • Koblenz, Germany
    • Recruiting
    • Gemeinschaftsklinikum Mittelrhein gGmbH - Koblenz Ev. Stift St. Martin
    • Contact: Niemann Dirk, MD; Email: Dirk.Niemann@gk.de
  • Köln, Germany
    • Not yet recruiting
    • Universitatsklinikum Koln
    • Contact: Heger Jan-Michel, MD; Email: jan-michel.heger@uk-koeln.de
  • Leipzig, Germany
    • Not yet recruiting
    • Universitätsklinikum Leipzig
    • Contact: Simone Heyn, MD; Email: Simone.Heyn@medizin.uni-leipzig.de
  • Luebeck, Germany
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
    • Contact: Nicolas von Bubnoff, MD; Email: nikolas.vonBubnoff@uksh.de
  • München, Germany
    • Not yet recruiting
    • Klinikum rechts der Isar TU München
    • Contact: Lena Illert, MD; Email: lena.illert@tum.de
  • Münster, Germany
    • Recruiting
    • Universitätsklinikum Münster
    • Contact: Andrea Kerkhoff, MD; Email: andrea.kerkhoff@ukmuenster.de
  • Nürnberg, Germany
    • Not yet recruiting
    • Universitätsklinik der Paracelsus Medizinischen Privatuniversität
    • Contact: Alexander Bott, MD; Email: alexander.bott@klinikum-nuernberg.de
  • Oldenburg, Germany
    • Recruiting
    • Pius-Hospital Oldenburg
    • Contact: Johannes Hoffmann, MD; Email: johannes.hoffmann@pius-hospital.de
  • Oldenburg In Holstein, Germany
    • Not yet recruiting
    • Klinikum Oldenburg gGmbH
    • Contact: Christoph Kimmich, MD; Email: kimmich.christoph@klinikum-oldenburg.de
  • Regensburg, Germany
    • Recruiting
    • Universitätsklinikum Regensburg
    • Contact: Florian Lüle, MD; Email: Florian.Lueke@klinik.uni-regensburg.de
  • Rostock, Germany
    • Not yet recruiting
    • Universitätsmedizin Rostock
    • Contact: Christoph Wittke, MD; Email: christoph.wittke@med.uni-rostock.de
  • Tübingen, Germany
    • Not yet recruiting
    • Universtitätsklinikum Tübingen
    • Contact: Robert Möhle, MD; Email: robert.moehle@med.uni-tuebingen.de
  • Ulm, Germany
    • Recruiting
    • Universitätsklinikum Ulm
    • Contact: Andreas Viardot, MD; Email: andreas.viardot@uniklinik-ulm.de
  • Villingen-Schwenningen, Germany
    • Recruiting
    • Schwarzwald-Baar-Klinikum Villingen-Schwenningen
    • Contact: Paul La Rosée, MD; Email: paul.laRosee@sbk-vs.de
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • Recruiting
      • University Hospital Freiburg, Department Medicine I, Hematology, oncology and stem cell transplantation
      • Contact: Elisabeth Schorb, MD; Phone Number: +4976127035360; Email: elisabeth.schorb@uniklinik-freiburg.de
      • Contact: Lisa K Isbell, MD; Email: lisa.isbell@uniklinik-freiburg.de
      • Contact: Florian Scherer, MD
      • Contact: Eliza Lauer, MD
    • Stuttgart, Baden-Wuerttemberg, Germany, 70174
      • Recruiting
      • Klinikum Stuttgart, Clinic of Hematology, Oncology and Palliative Care, Stuttgart Cancer Center / Tumor Center Eva Mayr-Stihl
      • Contact: Gerald Illerhaus, PhD; Phone Number: 30400 +49 711 278; Email: G.Illerhaus@klinikum-stuttgart.de
      • Contact: Julia Wendler, MD; Email: j.wendler@klinikum-stuttgart.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: R-MP and Procarbazine maintenance; Firstline systemic treatment with conventinal immunochemotherapy (3 cycles of Rituximab-MTX-Procarbazine) followed by Procarbazine maintenance
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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) between the 2 arms	PFS is defined as the time from randomization to disease progression or death of any cause, with censoring at the last date the patient was seen alive and free of disease progression	up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS) between the 2 arms	OS is defined as time from randomization until death from any cause, with censoring at the last date the patient was seen alive	up to 6 years
Event free survival (EFS) between the 2 arms	EFS, defined as time from randomization to premature end of treatment (EOT) due to any reason, lymphoma progression or death, whichever occurs first, with censoring at the last date the patient was seen event-free	up to 6 years
Remission status after 2 cycles of rituximab-methotrexate-procarbazine (R-MP) (arm A)/2 cycles of R-MTX/cytarabine (AraC)	Remission status after 2 cycles of RMP (arm A) / 2 cycles of R-MTX/AraC will be determined at response assessment (RA) I in both arms and will be divided in complete remission (CR), unconfirmed complete remission (CRu), partial remission (PR), stable disease (SD), progressive disease(PD) according to international PCNSL collaborative group (IPCG) criteria	at RA I: after 8 weeks (Arm A), after 6 weeks (Arm B)
Remission status after 3 cycles of R-MP (arm A)/consolidating HCT-ASCT (arm B)	determined at response assessment (RA) II and will be divided in CR, CRu, PR, SD, PD according to IPCG criteria	at RA II: after 12 weeks
Remission status after completion of maintenance treatment (arm A)/6 months follow-up (arm B)	will be determined 6 months after RA II and will be divided in CR, CRu, PR, SD, PD according to IPCG criteria	6 months after RA II
Quality of life (EORTC QLQ-C30)	EORTC quality of life questionnaire (QLQ)-C30 performed at screening, at RA II /premature EOT and thereafter every 12 months during follow-up	from date of informed consent form (ICF) signature up to 6 years
Quality of Life (EORTC-QLQ BN 20)	EORTC-QLQ brain neoplasm (BN) 20, performed at screening, at RA II /premature EOT and thereafter every 12 months during follow-up	from date of informed consent form (ICF) signature up to 6 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Toxicity	Incidence of (Serious) adverse events ((S)AE) as assessed by CTCAE v5.0	from date of informed consent form (ICF) signature until 30 days after end of treatment
Safety: Neurotoxicity	Results in the following neuropsychological tests: Montreal Cognitive Assessment (MoCA), Trail Making Test A and B, the Rey-Osterrieth-Complex-Figure-Test and a verbal fluency test, performed at screening, RA II / premature EOT and every 12 months during follow-up.	from date of informed consent form (ICF) signature up to 6 years
Unplanned hospital admissions	Defined as in-patient hospitalization due to SAE from date of informed consent form (ICF) signature until 30 days after ASCT or day 30 after last administration of IMP, whatever occurs first. Each hospitalization will be counted as a single event.	from date of informed consent form (ICF) signature until 30 days after ASCT or 30 days after last administration of investigational medicinal products (IMP)
Length of hospital stays	Measured as number of nights in hospital due to SAE as defined above, i.e. hospital stays from date of ICF signature until 30 days after ASCT or day 30 after last administration of IMP, whatever occurs first.	from date of informed consent form (ICF) signature until 30 days after ASCT or day 30 after last administration of IMP

Collaborators and Investigators

• Sponsor: University Hospital Freiburg
• Collaborators: German Federal Ministry of Education and Research; Heinrich-Heine University, Duesseldorf; University Hospital Tuebingen; University Hospital Munich; University Hospital Regensburg; Klinikum Stuttgart; University of Kaiserslautern

Publications and helpful links

General Publications

• Schorb E, Fox CP, Kasenda B, Linton K, Martinez-Calle N, Calimeri T, Ninkovic S, Eyre TA, Cummin T, Smith J, Yallop D, De Marco B, Krampera M, Trefz S, Orsucci L, Fabbri A, Illerhaus G, Cwynarski K, Ferreri AJM. Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice. Br J Haematol. 2020 Jun;189(5):879-887. doi: 10.1111/bjh.16451. Epub 2020 Jan 29.
• Schorb E, Isbell LK, Kerkhoff A, Mathas S, Braulke F, Egerer G, Roth A, Schliffke S, Borchmann P, Brunnberg U, Kroschinsky F, Mohle R, Rank A, Wellnitz D, Kasenda B, Pospiech L, Wendler J, Scherer F, Deckert M, Henkes E, von Gottberg P, Gmehlin D, Backenstrass M, Jensch A, Burger-Martin E, Grishina O, Fricker H, Malenica N, Orban A, Duyster J, Ihorst G, Finke J, Illerhaus G. High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial. Lancet Haematol. 2024 Mar;11(3):e196-e205. doi: 10.1016/S2352-3026(23)00371-X. Epub 2024 Jan 29.
• Mendez JS, Ostrom QT, Gittleman H, Kruchko C, DeAngelis LM, Barnholtz-Sloan JS, Grommes C. The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades. Neuro Oncol. 2018 Apr 9;20(5):687-694. doi: 10.1093/neuonc/nox187.
• Houillier C, Soussain C, Ghesquieres H, Soubeyran P, Chinot O, Taillandier L, Lamy T, Choquet S, Ahle G, Damaj G, Agape P, Molucon-Chabrot C, Amiel A, Delwail V, Fabbro M, Jardin F, Chauchet A, Moles-Moreau MP, Morschhauser F, Casasnovas O, Gressin R, Fornecker LM, Abraham J, Marolleau JP, Tempescul A, Campello C, Colin P, Tamburini J, Laribi K, Serrier C, Haioun C, Chebrek S, Schmitt A, Blonski M, Houot R, Boyle E, Bay JO, Oberic L, Tabouret E, Waultier A, Martin-Duverneuil N, Touitou V, Cassoux N, Kas A, Mokhtari K, Charlotte F, Alentorn A, Feuvret L, Le Garff-Tavernier M, Costopoulos M, Mathon B, Peyre M, Delgadillo D, Douzane H, Genet D, Aidaoui B, Hoang-Xuan K, Gyan E. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study. Neurology. 2020 Mar 10;94(10):e1027-e1039. doi: 10.1212/WNL.0000000000008900. Epub 2020 Jan 6.
• Olivier G, Clavert A, Lacotte-Thierry L, Gardembas M, Escoffre-Barbe M, Brion A, Cumin I, Legouffe E, Solal-Celigny P, Chabin M, Ingrand P, Colombat P, Delwail V. A phase 1 dose escalation study of idarubicin combined with methotrexate, vindesine, and prednisolone for untreated elderly patients with primary central nervous system lymphoma. The GOELAMS LCP 99 trial. Am J Hematol. 2014 Nov;89(11):1024-9. doi: 10.1002/ajh.23812. Epub 2014 Aug 27.
• Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosee PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Ruda R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gorlov JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG). Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. doi: 10.1016/S2352-3026(16)00036-3. Epub 2016 Apr 6.
• Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosee P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sonderskov Gorlov J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG). Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017 Nov;4(11):e510-e523. doi: 10.1016/S2352-3026(17)30174-6. Epub 2017 Oct 17.
• Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Mohle R, Low S, Binder M, Atta J, Keller U, Wolf HH, Krause SW, Hess G, Naumann R, Sasse S, Hirt C, Lamprecht M, Martens U, Morgner A, Panse J, Frickhofen N, Roth A, Hader C, Deckert M, Fricker H, Ihorst G, Finke J, Illerhaus G. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia. 2017 Apr;31(4):846-852. doi: 10.1038/leu.2016.334. Epub 2016 Nov 15.
• Schorb E, Kasenda B, Ihorst G, Scherer F, Wendler J, Isbell L, Fricker H, Finke J, Illerhaus G. High-dose chemotherapy and autologous stem cell transplant in elderly patients with primary CNS lymphoma: a pilot study. Blood Adv. 2020 Jul 28;4(14):3378-3381. doi: 10.1182/bloodadvances.2020002064.
• Schorb E, Finke J, Ihorst G, Kasenda B, Fricker H, Illerhaus G. Age-adjusted high-dose chemotherapy and autologous stem cell transplant in elderly and fit primary CNS lymphoma patients. BMC Cancer. 2019 Mar 29;19(1):287. doi: 10.1186/s12885-019-5473-z.
• Omuro A, Chinot O, Taillandier L, Ghesquieres H, Soussain C, Delwail V, Lamy T, Gressin R, Choquet S, Soubeyran P, Huchet A, Benouaich-Amiel A, Lebouvier-Sadot S, Gyan E, Touitou V, Barrie M, del Rio MS, Gonzalez-Aguilar A, Houillier C, Delgadillo D, Lacomblez L, Tanguy ML, Hoang-Xuan K. Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial. Lancet Haematol. 2015 Jun;2(6):e251-9. doi: 10.1016/S2352-3026(15)00074-5. Epub 2015 Jun 3.
• Wendler J, Fox CP, Valk E, Steinheber C, Fricker H, Isbell LK, Neumaier S, Okosun J, Scherer F, Ihorst G, Cwynarski K, Schorb E, Illerhaus G. Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma. BMC Cancer. 2022 Sep 10;22(1):971. doi: 10.1186/s12885-022-09723-w.
• Farhi J, Laribi K, Orvain C, Hamel JF, Mercier M, Sutra Del Galy A, Clavert A, Rousselet MC, Tanguy-Schmidt A, Hunault-Berger M, Moles-Moreau MP. Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma. Ann Hematol. 2018 Dec;97(12):2391-2401. doi: 10.1007/s00277-018-3468-5. Epub 2018 Aug 8.
• Martinez-Calle N, Isbell LK, Cwynarski K, Schorb E. Advances in treatment of elderly primary central nervous system lymphoma. Br J Haematol. 2022 Feb;196(3):473-487. doi: 10.1111/bjh.17799. Epub 2021 Aug 26.
• Schorb E, Isbell LK, Illerhaus G, Ihorst G, Meerpohl JJ, Grummich K, Nagavci B, Schmucker C. Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review. Cancers (Basel). 2021 Aug 24;13(17):4268. doi: 10.3390/cancers13174268.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2023
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2031

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: 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
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Antineoplastic Agents; Procarbazine
• Other Study ID Numbers: P003077; 2020-001181-10 (EudraCT Number); DRKS00024085 (Registry Identifier: German Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Publication of study protocol and publication of study results
• IPD Sharing Time Frame: year 2023 and after completion of study

IPD Sharing Access Criteria

Isbell LK et al. 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 - the randomized phase III PRIMA-CNS trial. BMC Cancer. 2023 Aug 18;23(1):767.

doi: 10.1186/s12885-023-11193-7. PMID: 37596517; PMCID: PMC10436648.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No