Clinical trial • Phase III • Oncology|Haematology

PROCARBAZINE for Primary central nervous system diffuse large B-cell lymphoma (PCNSL)

Phase III trial of PROCARBAZINE for Primary central nervous system diffuse large B-cell lymphoma (PCNSL).

Overview

Trial Therapeutic Area
Oncology|Haematology
Trial Disease
Primary central nervous system diffuse large B-cell lymphoma (PCNSL)
Trial Stage
Phase III
Drug Modality
Small molecule|Monoclonal antibody

Key dates

Initial CTIS Submission Date
18-07-2024
First CTIS Authorization Date
16-08-2024

Trial design

Randomised, open-label, arm a (control): r-mp — rituximab 375 mg/m² i.v. d0,14; methotrexate (mtx) 3.5 g/m² i.v. d1,15; procarbazine 60 mg/m²/d p.o. d2-11 — 3 cycles (28-day cycle) followed by maintenance procarbazine 100 mg absolute p.o. d1-5 for 6 cycles (28-day cycle). arm b (experimental): 2 cycles (21-day cycle) of rmtx/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 high-dose chemotherapy/autologous stem cell transplantation (hct-asct) with rituximab 375 mg/m² d-8, busulfan 3.2 mg/kg/d i.v. d-7 and d-6, thiotepa 5 mg/kg/d i.v. d-5 and d-4. Phase III trial in Austria, Germany.

Randomised
Yes
Open Label
Yes
Comparator
Arm A (control): R-MP — rituximab 375 mg/m² i.v. d0,14; methotrexate (MTX) 3.5 g/m² i.v. d1,15; procarbazine 60 mg/m²/d p.o. d2-11 — 3 cycles (28-day cycle) followed by maintenance procarbazine 100 mg absolute p.o. d1-5 for 6 cycles (28-day cycle). Arm B (experimental): 2 cycles (21-day cycle) of RMTX/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 high-dose chemotherapy/autologous stem cell transplantation (HCT-ASCT) with rituximab 375 mg/m² d-8, busulfan 3.2 mg/kg/d i.v. d-7 and d-6, thiotepa 5 mg/kg/d i.v. d-5 and d-4.
Target Sample Size
260

Eligibility

Recruits 260 Patients may be temporarily legally not competent due to their disease; written informed consent can be provided by the patient or by an authorized legal representative if the patient is temporarily legally not competent. Patients without legal capacity who do not have a designated legal representative are excluded..

Pregnancy Exclusion
19. Fertile patients refusing to use safe contraceptive methods during the study.
Vulnerable Population
Patients may be temporarily legally not competent due to their disease; written informed consent can be provided by the patient or by an authorized legal representative if the patient is temporarily legally not competent. Patients without legal capacity who do not have a designated legal representative are excluded.

Inclusion criteria

  • {"criterion_text":"- 1. Immunocompetent patients with newly-diagnosed primary DLBCL of the central nervous system."}
  • {"criterion_text":"- 2. Age > 70 years or age 65-70 years if not eligible for more intensive treatment (e.g. OptiMATe trial)."}
  • {"criterion_text":"- 3. Histologically or cytologically assessed diagnosis of B -cell lymphoma by local pathologist."}
  • {"criterion_text":"- 4. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy."}
  • {"criterion_text":"- 5. Disease exclusively located in the CNS."}
  • {"criterion_text":"- 6. At least 1 measurable lesion."}
  • {"criterion_text":"- 7. ECOG-Performance Status ≤2."}
  • {"criterion_text":"- 8. Patients possibly eligible for HCT-ASCT as judged by the treating physician."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Additional randomization criteria: 1. Patients eligible for HCT-ASCT defined by the EBL score (at most 1 of the 3 following conditions may apply: ECOG PS > 1, Barthel Index of ADL < 20 and Lachs geriatric screening > 3), improvement of PS after prephase treatment or clinical judgement by the treating physician after discussion with the study expert team."}
  • {"criterion_text":"- Additional randomization criteria: 2. No evidence of disease progression after pre-phase treatment."}

Exclusion criteria

  • {"criterion_text":"- 1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation."}
  • {"criterion_text":"- 2. Systemic lymphoma manifestation (outside the CNS)."}
  • {"criterion_text":"- 3. Primary vitreoretinal lymphoma or primary leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 5. Previous systemic Non-Hodgkin lymphoma at any time."}
  • {"criterion_text":"- 6. Inadequate renal function (creatinine clearance <60 ml/min)."}
  • {"criterion_text":"- 7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision."}
  • {"criterion_text":"- 8. Active hepatitis B or C disease."}
  • {"criterion_text":"- 9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with administration of study medication within the last 30 days before the start of this study."}
  • {"criterion_text":"- 10. Clinically relevant third space fluid accumulation according to the investigator's discretion."}
  • {"criterion_text":"- 11. Hypersensitivity to study treatment or any component of the formulation."}
  • {"criterion_text":"- 12. Taking any medications likely to cause interactions with the study medication."}
  • {"criterion_text":"- 13. Known or persistent abuse of medication, drugs or alcohol."}
  • {"criterion_text":"- 14. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic."}
  • {"criterion_text":"- 15. Patients without legal capacity and who are unable to understand the nature, significance and consequences of the study and without designated legal representative."}
  • {"criterion_text":"- 16. Previous participation in this trial."}
  • {"criterion_text":"- 17. Persons who are in a relationship of dependency/employment to the sponsor and/ or investigator."}
  • {"criterion_text":"- 18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule."}
  • {"criterion_text":"- 19. Fertile patients refusing to use safe contraceptive methods during the study."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Progression free survival","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Event free survival (EFS; defined as time from randomization to premature end of treatment (EOT) due to any reason, lymphoma progression or death, whichever occurs first)","definition_or_measurement_approach":"Defined in-text as: time from randomization to premature end of treatment (EOT) due to any reason, lymphoma progression or death, whichever occurs first."}
  • {"endpoint_text":"- Remission during and after induction treatment","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Remission after maintenance: 6 months after RAII","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Quality of life (QoL): EORTC QLQ-C30, EORTC QLQ-BN20; measured during screening period, at RAII and premature EOT visit and thereafter every 12 months during follow-up.","definition_or_measurement_approach":"Measured using EORTC QLQ-C30 and EORTC QLQ-BN20 at screening, at RAII, at premature EOT visit and annually during follow-up."}

Recruitment

Planned Sample Size
260
Recruitment Window Months
96
Consent Approach
Written informed consent is required according to international guidelines and local laws. Consent is provided by the patient or, if the patient is temporarily legally not competent due to their disease, by an authorized legal representative. Subject information and consent forms are available site-/country-specific (documents exist for Austria and Germany) and translations are provided (including German and Russian translations indicated in the document list).

Geography

Total Number Of Sites
38
Total Number Of Participants
260

Austria

Earliest CTIS Part Ii Submission Date
12-08-2024
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
613
Number Of Sites
5
Number Of Participants
12

Sites

Site Name
University Hospital Graz
Department Name
Klinische Abteilung für Hämatologie
Contact Person Name
Annkristin Heine
Contact Person Email
annkristin.heine@medunigraz.at
Site Name
Hanusch Krankenhaus Der Wiener Gebietskrankenkasse
Department Name
3. Medizinischen Abteilung Hämatologie & Onkologie
Contact Person Name
Alexandra Böhm
Contact Person Email
alexandra.boehm@oegk.at
Site Name
Johannes Kepler University Linz
Department Name
Univ.-Klinik für Hämatologie und Internistische Onkologie Med Campus III.
Contact Person Name
Clemens Schmitt
Site Name
Medizinische Universitaet Innsbruck
Department Name
Universitätsklinik für Innere Medizin V
Contact Person Name
Dominik Wolf
Contact Person Email
dominik.wolf@i-med.ac.at
Site Name
Ordensklinikum Linz GmbH
Department Name
Zentrum für Hämatologie und Stammzelltransplantation, Hämostaseologie und medizinische Onkologie
Contact Person Name
Dagmar Wipplinger

Germany

Earliest CTIS Part Ii Submission Date
12-08-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
610
Number Of Sites
33
Number Of Participants
248

Sites

Site Name
Gemeinschaftsklinikum Mittelrhein gGmbH
Department Name
Klinik für Innere Medizin
Contact Person Name
Dirk Niemann
Contact Person Email
Dirk.Niemann@gk.de
Site Name
Goethe University Frankfurt
Department Name
Medizinische Klinik III Hämatologie und Onkologie
Contact Person Name
Thomas Oellerich
Contact Person Email
oellerich@em.uni-frankfurt.de
Site Name
Johannes Gutenberg University Mainz
Department Name
III. Medizinische Klinik und Poliklinik
Contact Person Name
Georg Heß
Contact Person Email
georg.hess@unimedizin-mainz.de
Site Name
Medical Center - University Of Freiburg
Department Name
Medizinische Klinik I Hämatologie/Onkologie u. Stammzelltransplantation
Contact Person Name
Elisabeth Schorb
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Hämatologie
Contact Person Name
Bastian von Tresckow
Site Name
Universitaetsklinikum Leipzig AöR
Department Name
Med. Klinik und Poliklinik I - Hämatologie und Zelltherapie, Internistische Onkologie, Hämostaseolog
Contact Person Name
Simone Heyn
Site Name
Universitaetsklinikum Magdeburg AöR
Department Name
Klinik fuer Hamatologie und Onkologie
Contact Person Name
Vanja Zeremski
Contact Person Email
vanja.zeremski@med.ovgu.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Klinik für Hämatologie und Medizinische Onkologie
Contact Person Name
Justin Hasenkamp
Site Name
HELIOS Klinikum Berlin-Buch GmbH
Department Name
Hämatologie und Stammzelltransplantation
Contact Person Name
Julia Pross
Site Name
LMU Klinikum Muenchen AöR
Department Name
Medizinische Klinik und Poliklinik III Hämatologie/Onkologie
Contact Person Name
Martin Dreyling
Site Name
Klinikum Chemnitz gGmbH
Department Name
Klinik für Innere Medizin III Hämatologie, Onkologie, Stammzelltransplantation
Contact Person Name
Mathias Hänel
Contact Person Email
m.haenel@skc.de
Site Name
Barmherzige Brueder Trier gGmbH
Department Name
Hämatologie und Onkologie Innere Medizin I
Contact Person Name
Iordanis Deligiannis
Contact Person Email
i.deligiannis@bbtgruppe.de
Site Name
Universitaet Des Saarlandes
Department Name
Innere Medizin I
Contact Person Name
Lorenz Thurner
Contact Person Email
lorenz.thurner@uks.eu
Site Name
Staedtisches Klinikum Braunschweig gGmbH
Department Name
Medizinische Klinik III Hämatologie und Onkologie
Contact Person Name
Jürgen Krauter
Contact Person Email
j.krauter@skbs.de
Site Name
Barmherzige Brueder gemeinnuetzige Krankenhaus GmbH
Department Name
Klinik für Onkologie und Hämatologie
Contact Person Name
Veronika Berberich
Site Name
Rostock University Medical Center
Department Name
ulrich.langenkamp@med.uni-rostock.de
Contact Person Name
Ulrich Langenkamp
Site Name
Technische Universitaet Dresden
Department Name
Medizinische Klinik I und Poliklinik
Contact Person Name
Frank Kroschinsky
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
III. Med. Klinik und Poliklinik Hämatologie u. Internistische Onkologi
Contact Person Name
Maike Hefter
Contact Person Email
maike.hefter@mri.tum.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Med. Kl. M. S. Hämatologie, Onkologie und Tumorimmunologie
Contact Person Name
Ulrich Keller
Contact Person Email
ulrich.keller@charite.de
Site Name
Universitaetsklinikum Augsburg
Department Name
II. Medizinische Klinik Cancer Center Augsburg
Contact Person Name
Mathias Lutz
Contact Person Email
mathias.lutz@uk-augsburg.de
Site Name
Universitaetsklinikum Knappschaftskrankenhaus Bochum GmbH
Department Name
Neurologische Klinik
Contact Person Name
Sabine Seidel
Contact Person Email
Sabine.Seidel@kk-bochum.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Innere Medizin III Hämatologie, Onkologie, Rheumatologie und Infektionskrankheiten
Contact Person Name
Andreas Viardot
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Klinik für Onkologie, Hämatologie und Stammzelltransplantation (Medizinische Klinik IV)
Contact Person Name
Jens Panse
Contact Person Email
jpanse@ukaachen.de
Site Name
Barmherzige Brueder Trier gGmbH (duplicate listing in Germany block?)
Department Name
Hämatologie und Onkologie Innere Medizin I
Contact Person Name
Iordanis Deligiannis
Contact Person Email
i.deligiannis@bbtgruppe.de
Site Name
Klinikum Der Landeshauptstadt Stuttgart gKAöR
Department Name
Interdisziplinäre internistische Onkologie, Hämatologie und Palliativmedizin
Contact Person Name
Gerald Illerhaus
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Medizinische Klinik A Hämatologie und Onkologie
Contact Person Name
Evgenii Shumilov
Contact Person Email
evgenii.shumilov@ukmuenster.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Medizinische Klinik II Onkologisches Zentrum
Contact Person Name
Minna Voigtländer
Contact Person Email
m.voigtlaender@uke.de
Site Name
Klinikum Nuernberg
Department Name
Klinik für Innere Medizin 5 Schwerpunkt Onkologie/Hämatologie
Contact Person Name
Alexander Bott
Site Name
Universitaetsklinikum Regensburg AöR
Department Name
Klinik & Poliklinik für Innere Medizin III Hämatologie & Onkologie
Contact Person Name
Florian Lüke
Site Name
Diakonie in Suedwestfalen gGmbH
Department Name
Abteilung Medizinische Klinik III
Contact Person Name
Ralph Naumann
Contact Person Email
Ralph.Naumann@diakonie-sw.de
Site Name
Martin-Luther-Universitaet Halle-Wittenberg
Department Name
Klinik und Poliklinik für Innere Medizin IV Onkologie/Hämatologie
Contact Person Name
Thomas Weber
Contact Person Email
thomas.weber@uk-halle.de
Site Name
University Hospital Cologne AöR
Department Name
Klinikum I für Innere Medizin
Contact Person Name
Jan-Michel Heger
Contact Person Email
jan-michel.heger@uk-koeln.de
Site Name
Klinikum Bielefeld gGmbH
Department Name
Onkologie/Hämatologie /Palliativmedizin
Contact Person Name
Kai Wegehenkel
Site Name
Universitaetsklinikum Schleswig-Holstein AöR (Lübeck site)
Department Name
Klinik für Hämatologie und Onkologie
Contact Person Name
Nikolas von Bubnoff
Contact Person Email
nikolas.vonBubnoff@uksh.de
Site Name
Staedtisches Klinikum Karlsruhe gGmbH
Department Name
III. Medizin Hämatologie/Onkologie
Contact Person Name
Martin Bentz
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Klinik für Hämatologie, Onkologie und Klinische Immunologie
Contact Person Name
Birte Friedrichs
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Medizinische Klinik 5 Hämatologie und Internistische Onkologie
Contact Person Name
Bernd Spriewald
Contact Person Email
bernd.spriewald@uk-erlangen.de
Site Name
Gesundheit Nord gGmbH Klinikverbund Bremen
Department Name
Medizinische Klinik I
Contact Person Name
Maher Hanoun
Contact Person Email
maher.hanoun@gesundheitnord.de
Site Name
Pius-Hospital Oldenburg
Department Name
Abteilung für internistische Onkologie
Contact Person Name
Johannes Hoffmann
Site Name
Klinikum Oldenburg AöR
Department Name
Abt. Onkologie/Hämatologie
Contact Person Name
Christoph Kimmich
Site Name
Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH
Department Name
Klinik für Innere Medizin II
Contact Person Name
Paul Graf La Rosée
Contact Person Email
paul.laRosee@sbk-vs.de

Sponsor

Primary sponsor

Full Name
Medical Center - University Of Freiburg
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Germany

Third parties

  • {"country":"Germany","full_name":"Federal Ministry for Education and Research in Germany","duties_or_roles":"Source of monetary support","organisation_type":"Government"}

Investigational products

Investigational Product Name
PROCARBAZINE
Active Substance
PROCARBAZINE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Starting Dose
60 mg/m²/day (p.o.) (induction); maintenance procarbazine 100 mg absolute/day (p.o.)
Frequency
d2-11 (induction), maintenance d1-5 of 28-day cycles
Maximum Dose
60
Investigational Product Name
BUSULFAN
Active Substance
BUSULFAN
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Starting Dose
3.2 mg/kg/day i.v.
Frequency
d-7 and d-6 (conditioning)
Maximum Dose
3.2
Investigational Product Name
THIOTEPA
Active Substance
THIOTEPA
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Starting Dose
5 mg/kg/day i.v.
Frequency
d-5 and d-4 (conditioning)
Maximum Dose
5
Investigational Product Name
RITUXIMAB
Active Substance
RITUXIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Starting Dose
375 mg/m² i.v.
Frequency
d0 and d14 (R-MP) or d0 and d4 (RMTX/AraC); also d-8 in conditioning
Maximum Dose
375
Investigational Product Name
CARMUSTINE
Active Substance
CARMUSTINE
Modality
Small molecule
Routes Of Administration
Intravenous (powder for solution for infusion)
Route
Intravenous
Maximum Dose
400
Investigational Product Name
CYTARABINE
Active Substance
CYTARABINE (AraC)
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Starting Dose
2 x 2 g/m² i.v.
Frequency
AraC 2x2 g/m² i.v. on d2 + d3 (per protocol for Arm B)
Maximum Dose
4
Investigational Product Name
METHOTREXATE DISODIUM
Active Substance
METHOTREXATE DISODIUM
Modality
Small molecule
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Starting Dose
3.5 g/m² i.v.
Frequency
Pre-phase: MTX 3.5 g/m² i.v. d1; R-MP cycles: MTX 3.5 g/m² i.v. d1,15
Maximum Dose
3.5
Combination Treatment
Yes

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