Diffuse Large B-cell-lymphomaPhase 3MATRixNCT02531841
High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma
A Phase 3 study testing Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®) and Arm B (TEPADINA®-CARMUBRIS®-Busilvex®) in people with Diffuse Large B-cell-lymphoma, run by University Hospital Freiburg at 2 sites in Germany.
Trial summary
In the presently planned multicentre Phase III trial the two therapies will be compared: Patients will be randomized after intensified induction treatment with 4 cycles rituximab, methotrexate, cytarabine and thiotepa (MATRix) between first-line high-dose chemotherapy against conventional consolidating therapy with 2… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diffuse Large B-cell-lymphoma
- What is being tested?
- Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®) and Arm B (TEPADINA®-CARMUBRIS®-Busilvex®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 2 sitesGermany
- Study dates
- Jul 2014to Dec 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Immunocompetent patients with newly-diagnosed primary central nervous system B-cell lymphoma
- Age 18-65 years irrespective of ECOG or 66-70 years (with ECOG Performance Status ≤2)
- Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist.
- Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
- Disease exclusively located in the CNS
- At least one measurable lesion
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- Previously untreated patients (previous or ongoing steroid treatment admitted)
- Sexually active patients of childbearing potential who agree to take adequate contraceptive measures during study participation
- 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
- Sufficient stem cell harvest (≥ 5 x 106 CD34+ cells/kg of body weight)
- Complete remission, unconfirmed complete remission or partial remission
- Central pathology results confirming local results
Who cannot join
- Congenital or acquired immunodeficiency
- Systemic lymphoma manifestation (outside the CNS)
- Isolated ocular lymphoma without manifestation in the brain parenchyma or spinal cord
- Previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years
- Previous Non-Hodgkin lymphoma at any time
- Inadequate bone marrow (platelet count decreased ≥CTC grade 1, anemia ≥CTC grade 1, neutrophil count decreased ≥CTC grade 1), renal (creatinine clearance <60 ml/min), cardiac (ejection fraction decreased ≥CTC grade 2), or hepatic function (blood bilirubin increased ≥CTC grade 2, alanine aminotransferase increased ≥CTC grade 2, aspartate aminotransferase increased ≥CTC grade 2 or gamma-GT increased ≥CTC grade 2)
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- HBsAg, anti-HBc or HCV positivity
- HIV infection, previous organ transplantation or other clinical evident form of immunodeficiency
- Concurrent treatment with other experimental drugs or participation in a clinical trial within the last thirty days before the start of this study
- Symptomatic coronary artery disease, cardiac arrhythmias uncontrolled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease)
- Severe non-compensated pulmonary disease (IVC <55%, DLCO <40%)
- Third space fluid accumulation >500 ml
- Hypersensitivity to study treatment or any component of the formulation
- Taking any medications likely to cause interactions with the study medication
- Known or persistent abuse of medication, drugs or alcohol
- Patient without legal capacity and who is unable to understand the nature, significance and consequences of the study and without designated legal representative
- Persons who are in a relationship of dependency/employment to the sponsor and/ or investigator
- Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Concurrent (or planned) pregnancy or lactation
- Fertile patients refusing to use safe contraceptive methods during the study
Trial locations and contacts
2 sites in 1 country.
Germany2 sites, 2 recruiting
- Recruiting
University Hospital Freiburg - Department for Hematology, Oncology and Stem cell Transplantion
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Juergen Finke, PhD, +49761270 ext. 34080, juergen.finke@uniklinik-freiburg.de
Elisabeth Schorb, PhD, +49761270 ext. 33210, elisabeth.schorb@uniklinik-freiburg.de
- Recruiting
Klinikum Stuttgart, Clinic of Hematology, Oncology and Palliative Care, Stuttgart Cancer Center / Tumor Center Eva Mayr-Stihl
Stuttgart, Baden-Wurttemberg, 70174
Gerald Illerhaus, PhD, +49 711 278 ext. 30400, G.Illerhaus@klinikum-stuttgart.de
Kristina Mikesch, PhD, +49 711 278 ext. 30403, k.mikesch@klinikum-stuttgart.de
About this study
Official title: High-dose Chemotherapy and Autologous Stem Cell Transplant or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma - Randomized Phase III Trial
In the presently planned multicentre Phase III trial the two therapies will be compared: Patients will be randomized after intensified induction treatment with 4 cycles rituximab, methotrexate, cytarabine and thiotepa (MATRix) between first-line high-dose chemotherapy against conventional consolidating therapy with 2 cycles of conventional chemotherapy with R-DeVIC (rituximab, dexamethasone, etoposide, ifosfamide, carboplatin).
Read the detailed description
Trial purpose and rationale Primary central nervous system lymphoma (PCNSL) is a highly aggressive disease with rising incidence over the past 30 years. Similar to other hematological diseases, the rationale for consolidation in PCNSL is the elimination of minimal residual disease. The efficacy of WBRT, which is the current standard for consolidation after HD-MTX-based systemic treatment, is being compared to HDT-ASCT in the ongoing IELSG-32 trial.
High-dose chemotherapy with carmustine or busulfan and thiotepa followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed eligible patients, but also in the salvage situation.
The question we aim to answer is whether HDT-ASCT is superior to conventional therapy as consolidation after intensified immunochemotherapy in newly diagnosed PCNSL.
Rationale for this study:
Based on previously obtained good results from the treatment of recurrent or refractory PCNSL the DeVIC protocol was chosen for conventional consolidation treatment. This protocol, originally designed as a salvage protocol for aggressive NHL, crosses the blood-brain barrier and consists of multidrug resistant unrelated agents.
Treatment plan and procedure
Interventions
Induction treatment 4 cycles (every 3 weeks), stem-cell harvest after 2nd cycle:
- Rituximab 375 mg/m²/d i.v. (d 0,5)
- Methotrexate 3,5 g/m² i.v. (d1)
- Cytarabine 2 x 2 g/m²/d i.v. (d2-3)
- Thiotepa 30 mg/m² i.v. (d4)
Patients with PD after two cycles, SD/PD after four cycles of induction therapy or insufficient stem-cell harvest after three cycles are ineligible for randomization.
Consolidation Arm A 2 cycles of R-DeVIC (every 3 weeks):
- Rituximab 375 mg/m²/d i.v. (d0)
- Dexamethasone 40 mg/d i.v. (d1-3)
- Etoposide 100 mg/m²/d i.v. (d1-3)
- Ifosfamide 1500 mg/m²/d i.v. (d1-3)
- Carboplatin 300 mg/m² i.v. (d1)
Consolidation Arm B
High-dose chemotherapy (HDT-ASCT):
- Carmustine* 400 mg/m² i.v. (d-6)
- Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
- Autologous Stem Cell Transplantation (d0)
- if carmustine is not available at the investigation site, busulfan can be administered instead:
- Busulfan 3,2 mg/kg/d (d-8-(-7))
- Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
- Autologous Stem Cell Transplantation (d0)
- Conditions
- Diffuse Large B-cell-lymphoma
- Being tested
- Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®), Arm B (TEPADINA®-CARMUBRIS®-Busilvex®)
- Medical subject headings
- Dendritic Cell Sarcoma, Interdigitating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®)Drug
Also called Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®
Arm A 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle:
- Rituximab 375 mg/m²/d i.v. (d0,5)
- Methotrexate 3.5 g/m² i.v. (d1)
- Cytarabine 2 x 2 g/m²/d i.v. (d2-3)
- Thiotepa 30 mg/m² i.v. (d4) Consolidation 2 cycles of R-DeVIC (every 3 weeks):
- Rituximab 375 mg/m²/d i.v. (d0)
- Dexamethasone 40 mg/d i.v. (d1-3)
- Etoposide 100 mg/m²/d i.v. (d1-3)
- Ifosfamide 1500 mg/m²/d i.v. (d1-3)
- Carboplatin 300 mg/m² i.v. (d1)
Arm B (TEPADINA®-CARMUBRIS®-Busilvex®)Drug
Also called TEPADINA®-CARMUBRIS®-Busilvex®
4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle:
- Rituximab 375 mg/m²/d i.v. (d0,5)
- Methotrexate 3.5 g/m² i.v. (d1)
- Cytarabine 2 x 2 g/m²/d i.v. (d2-3)
- Thiotepa 30 mg/m² i.v. (d4) Consolidation
High-dose chemotherapy (HDT-ASCT):
- Carmustine* 400 mg/m² i.v. (d-6)
- Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
- Autologous Stem Cell Transplantation (d0)
- if carmustine is not available at the investigation site, busulfan can be administered instead:
- Busulfan 3,2 mg/kg/d (d-8-(-7))
- Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
- Autologous Stem Cell Transplantation (d0)
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Induction Treatment 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle:
* Rituximab 375 mg/m²/d i.v. (d0,5)
* Methotrexate 3.5 g/m² i.v. (d1)
* Cytarabine 2 x 2 g/m²/d i.v. (d2-3)
* Thiotepa 30 mg/m² i.v. (d4)
Consolidation Treatment 2 cycles of R-DeVIC (every 3 weeks):
* Rituximab 375 mg/m²/d i.v. (d0)
* Dexamethasone 40 mg/d i.v. (d1-3)
* Etoposide 100 mg/m²/d i.v. (d1-3)
* Ifosfamide 1500 mg/m²/d i.v. (d1-3)
* Carboplatin 300 mg/m² i.v. (d1) Receives: Drug: Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®) |
| Arm B | Active comparator | Induction Treatment 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle:
* Rituximab 375 mg/m²/d i.v. (d0,5)
* Methotrexate 3.5 g/m² i.v. (d1)
* Cytarabine 2 x 2 g/m²/d i.v. (d2-3)
* Thiotepa 30 mg/m² i.v. (d4)
Consolidation Treatment High-dose chemotherapy
* Carmustine* 400 mg/m² i.v. (d-6)
* Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
* Autologous Stem Cell Transplantation (d0)
*if not available at study site, Busulfan can be administered instead:
* Busulfan 3,2 mg/kg/d i.v. (d-8-(-7))
* Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
* Autologous Stem Cell Transplantation (d0) Receives: Drug: Arm B (TEPADINA®-CARMUBRIS®-Busilvex®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure PFS will be measured by the number of events (PD, relapse or death from any cause) within the treatment arms
Progression-free survival PFS:
Response Assessment III at the end of study treatment (EOT) visit and every imaging diagnostic assessments during follow-up period: during year 1-2: every 3 month
Measured: PFS is defined as the time from randomization until PD or relapse or death from any cause up to 24 months after end of treatment
Secondary outcomes (6)
The secondary outcome measure CR will be assessed on day 60 after randomization using the IPCG response criteria
Response will be measured by the IPCG response criteria.
Measured: CR will be determined on day 60 after randomization
The secondary outcome measure Response duration will be measured by the time from CR, CRu or PR until relapse or PD using the IPCG response criteria
Response duration observation times for patients where the event of interest was not observed, will be censored at the time last seen alive. Timepoints of evaluation are defined as every assessment during follow up period in accordance with the protocol.
year 1-2: every 3 month
Measured: Time from CR, CRu or PR until relapse or PD up to 24 months after end of treatment
The secondary outcome OS is measured as time from randomization until death of any cause
Timepoints of evaluation are defined as every assessment during follow up period in accordance with the protocol.
year 1-2: every 3 month
Measured: OS is defined as time from randomization until death of any cause up to 24 months after end of treatment
Number of patients with (Serious) adverse events as assessed by CTCAE v4.0
After this time period, only SAEs judged by the investigator to be related to at least one of investigational products will be reported
Measured: All SAEs that occur starting from the first administration of the study medication until day 60 after randomization.
Number of patients with treatment related toxicity as assessed by CTCAE v4.0
If an abnormal parameter is not listed in the toxicity table, an AE must be documented
Measured: All toxicities that occur starting from the first administration of the study medication until day 60 after randomization.
Number of patients with neurotoxicity assessed by MMSE, EORTC QLQ-BN20 and the neuro-psychological battery
Timepoints of evaluation are defined as every assessment during follow up period in accordance with the protocol
Measured: All parameters of neurotoxicity that occur starting from the first administration of the study medication up to 24 months after end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2015 (estimated)
- Study startJul 2014
- Primary completionNov 2017 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell-lymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Freiburg
- Sponsor type
- University, hospital or other
- Collaborators
- German Federal Ministry of Education and Research, International Extranodal Lymphoma Study Group (IELSG)
- Responsible party
- Principal investigator, Elisabeth Schorb, University Hospital Freiburg
- Investigators
- Gerald Illerhaus, PhD, Principal investigator, Representative of Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02531841
- Sponsor's protocol ID
- DRKS00005503
- Acronym
- MATRix
- Status last verified
- Aug 2015
- First submitted
- 14 Aug 2015
- Last updated
- 25 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. doi: 10.1200/JCO.2006.06.2117. Epub 2006 Jul 24.
PubMed 16864853Illerhaus G, Muller F, Feuerhake F, Schafer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. doi: 10.3324/haematol.11771.
PubMed 18166803Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-2675. doi: 10.1093/annonc/mds059. Epub 2012 Apr 3.
PubMed 22473593Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. doi: 10.1200/JCO.2007.13.5533. Epub 2008 Apr 14.
PubMed 18413641Motomura K, Natsume A, Fujii M, Ito M, Momota H, Wakabayashi T. Long-term survival in patients with newly diagnosed primary central nervous system lymphoma treated with dexamethasone, etoposide, ifosfamide and carboplatin chemotherapy and whole-brain radiation therapy. Leuk Lymphoma. 2011 Nov;52(11):2069-75. doi: 10.3109/10428194.2011.596967. Epub 2011 Jul 12.
PubMed 21745167Illerhaus G, Ferreri AJM, Wendler J, Binder M, Borchmann P, Hasenkamp J, Stilgenbauer S, Roth A, Egerer G, Ernst T, Weber T, Hertenstein B, Lenz G, Dreyling M, Mohle R, Kobbe G, Schmidt CA, Brunnberg U, Panse J, Kneba M, Heinicke T, Schroll S, Larsen TS, Thurner L, Pukrop T, Salwender H, Naumann R, Hess G, Kroschinsky FP, Blystad AK, Keller U, Pulczynski EJ, Pedersen MB, Re F, Orsucci L, Pospiech L, La Rosee P, Deckert M, Ponzoni M, Gmehlin D, Backenstrass M, Jensch A, Valk E, Calimeri T, Kasenda B, Trepel M, Fricker H, Semenova I, Scherer F, von Gottberg P, Burger E, Grishina O, Hader C, Ihorst G, Finke J, Zucca E, Schorb E. High-dose chemotherapy followed by autologous stem-cell transplantation versus non-myeloablative consolidation in primary CNS lymphoma (MATRix/IELSG43): a randomised phase 3 trial. Lancet. 2026 Aug 8;408(10554):532-544. doi: 10.1016/S0140-6736(26)00917-7. Epub 2026 Jul 22.
PubMed 42486133Schorb E, Finke J, Ferreri AJ, Ihorst G, Mikesch K, Kasenda B, Fritsch K, Fricker H, Burger E, Grishina O, Valk E, Zucca E, Illerhaus G. High-dose chemotherapy and autologous stem cell transplant compared with conventional chemotherapy for consolidation in newly diagnosed primary CNS lymphoma--a randomized phase III trial (MATRix). BMC Cancer. 2016 Apr 21;16:282. doi: 10.1186/s12885-016-2311-4.
PubMed 27098429
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-dose Chemotherapy and Autologous Stem Cell Transplant or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma - Randomized Phase III Trial
- ClinicalTrials.gov ID
- NCT02531841
- Acronym / sponsor ID
- MATRix / DRKS00005503
- Conditions
- Diffuse Large B-cell-lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- University Hospital FreiburgUniversity, hospital or other
- Collaborators
- German Federal Ministry of Education and Research, International Extranodal Lymphoma Study Group (IELSG)
- Study start
- Jul 2014
- Primary completion
- Nov 2017 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 25 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the presently planned multicentre Phase III trial the two therapies will be compared: Patients will be randomized after intensified induction treatment with 4 cycles rituximab, methotrexate, cytarabine and thiotepa (MATRix) between first-line high-dose chemotherapy against conventional consolidating therapy with 2 cycles of conventional chemotherapy with R-DeVIC (rituximab, dexamethasone, etoposide, ifosfamide, carboplatin).
Detailed description
Trial purpose and rationale Primary central nervous system lymphoma (PCNSL) is a highly aggressive disease with rising incidence over the past 30 years. Similar to other hematological diseases, the rationale for consolidation in PCNSL is the elimination of minimal residual disease. The efficacy of WBRT, which is the current standard for consolidation after HD-MTX-based systemic treatment, is being compared to HDT-ASCT in the ongoing IELSG-32 trial.
High-dose chemotherapy with carmustine or busulfan and thiotepa followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed eligible patients, but also in the salvage situation.
The question we aim to answer is whether HDT-ASCT is superior to conventional therapy as consolidation after intensified immunochemotherapy in newly diagnosed PCNSL.
Rationale for this study:
Based on previously obtained good results from the treatment of recurrent or refractory PCNSL the DeVIC protocol was chosen for conventional consolidation treatment. This protocol, originally designed as a salvage protocol for aggressive NHL, crosses the blood-brain barrier and consists of multidrug resistant unrelated agents.
Treatment plan and procedure
Interventions
Induction treatment 4 cycles (every 3 weeks), stem-cell harvest after 2nd cycle:
- Rituximab 375 mg/m²/d i.v. (d 0,5)
- Methotrexate 3,5 g/m² i.v. (d1)
- Cytarabine 2 x 2 g/m²/d i.v. (d2-3)
- Thiotepa 30 mg/m² i.v. (d4)
Patients with PD after two cycles, SD/PD after four cycles of induction therapy or insufficient stem-cell harvest after three cycles are ineligible for randomization.
Consolidation Arm A 2 cycles of R-DeVIC (every 3 weeks):
- Rituximab 375 mg/m²/d i.v. (d0)
- Dexamethasone 40 mg/d i.v. (d1-3)
- Etoposide 100 mg/m²/d i.v. (d1-3)
- Ifosfamide 1500 mg/m²/d i.v. (d1-3)
- Carboplatin 300 mg/m² i.v. (d1)
Consolidation Arm B
High-dose chemotherapy (HDT-ASCT):
- Carmustine* 400 mg/m² i.v. (d-6)
- Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
- Autologous Stem Cell Transplantation (d0)
- if carmustine is not available at the investigation site, busulfan can be administered instead:
- Busulfan 3,2 mg/kg/d (d-8-(-7))
- Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4))
- Autologous Stem Cell Transplantation (d0)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®)Induction Treatment 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation Treatment 2 cycles of R-DeVIC (every 3 weeks): * Rituximab 375 mg/m²/d i.v. (d0) * Dexamethasone 40 mg/d i.v. (d1-3) * Etoposide 100 mg/m²/d i.v. (d1-3) * Ifosfamide 1500 mg/m²/d i.v. (d1-3) * Carboplatin 300 mg/m² i.v. (d1) |
| Arm B | Active comparator | Drug: Arm B (TEPADINA®-CARMUBRIS®-Busilvex®)Induction Treatment 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation Treatment High-dose chemotherapy * Carmustine* 400 mg/m² i.v. (d-6) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) *if not available at study site, Busulfan can be administered instead: * Busulfan 3,2 mg/kg/d i.v. (d-8-(-7)) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Immunocompetent patients with newly-diagnosed primary central nervous system B-cell lymphoma
- Age 18-65 years irrespective of ECOG or 66-70 years (with ECOG Performance Status ≤2)
- Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist.
- Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
- Disease exclusively located in the CNS
Key exclusion criteria (20 listed)
- Congenital or acquired immunodeficiency
- Systemic lymphoma manifestation (outside the CNS)
- Isolated ocular lymphoma without manifestation in the brain parenchyma or spinal cord
- Previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years
- Previous Non-Hodgkin lymphoma at any time
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®)Also: Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®Arm A 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation 2 cycles of R-DeVIC (every 3 weeks): * Rituximab 375 mg/m²/d i.v. (d0) * Dexamethasone 40 mg/d i.v. (d1-3) * Etoposide 100 mg/m²/d i.v. (d1-3) * Ifosfamide 1500 mg/m²/d i.v. (d1-3) * Carboplatin 300 mg/m² i.v. (d1) | Drug | Arm A |
| Arm B (TEPADINA®-CARMUBRIS®-Busilvex®)Also: TEPADINA®-CARMUBRIS®-Busilvex®4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation High-dose chemotherapy (HDT-ASCT): * Carmustine* 400 mg/m² i.v. (d-6) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) * if carmustine is not available at the investigation site, busulfan can be administered instead: * Busulfan 3,2 mg/kg/d (d-8-(-7)) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) | Drug | Arm B |
Primary outcome
The primary outcome measure PFS will be measured by the number of events (PD, relapse or death from any cause) within the treatment arms
Time frame: PFS is defined as the time from randomization until PD or relapse or death from any cause up to 24 months after end of treatment
Progression-free survival PFS: Response Assessment III at the end of study treatment (EOT) visit and every imaging diagnostic assessments during follow-up period: during year 1-2: every 3 month
6 secondary outcomes
The secondary outcome measure CR will be assessed on day 60 after randomization using the IPCG response criteria
Time frame: CR will be determined on day 60 after randomization
The secondary outcome measure Response duration will be measured by the time from CR, CRu or PR until relapse or PD using the IPCG response criteria
Time frame: Time from CR, CRu or PR until relapse or PD up to 24 months after end of treatment
The secondary outcome OS is measured as time from randomization until death of any cause
Time frame: OS is defined as time from randomization until death of any cause up to 24 months after end of treatment
Number of patients with (Serious) adverse events as assessed by CTCAE v4.0
Time frame: All SAEs that occur starting from the first administration of the study medication until day 60 after randomization.
Number of patients with treatment related toxicity as assessed by CTCAE v4.0
Time frame: All toxicities that occur starting from the first administration of the study medication until day 60 after randomization.
Number of patients with neurotoxicity assessed by MMSE, EORTC QLQ-BN20 and the neuro-psychological battery
Time frame: All parameters of neurotoxicity that occur starting from the first administration of the study medication up to 24 months after end of treatment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2015.
- Results publication: PubMed 16864853Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. doi: 10.1200/JCO.2006.06.2117. Epub 2006 Jul 24.
- Results publication: PubMed 18166803Illerhaus G, Muller F, Feuerhake F, Schafer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. doi: 10.3324/haematol.11771.
- Results publication: PubMed 22473593Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-2675. doi: 10.1093/annonc/mds059. Epub 2012 Apr 3.
- Results publication: PubMed 18413641Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. doi: 10.1200/JCO.2007.13.5533. Epub 2008 Apr 14.
- Results publication: PubMed 21745167Motomura K, Natsume A, Fujii M, Ito M, Momota H, Wakabayashi T. Long-term survival in patients with newly diagnosed primary central nervous system lymphoma treated with dexamethasone, etoposide, ifosfamide and carboplatin chemotherapy and whole-brain radiation therapy. Leuk Lymphoma. 2011 Nov;52(11):2069-75. doi: 10.3109/10428194.2011.596967. Epub 2011 Jul 12.
- Derived from this study: PubMed 42486133Illerhaus G, Ferreri AJM, Wendler J, Binder M, Borchmann P, Hasenkamp J, Stilgenbauer S, Roth A, Egerer G, Ernst T, Weber T, Hertenstein B, Lenz G, Dreyling M, Mohle R, Kobbe G, Schmidt CA, Brunnberg U, Panse J, Kneba M, Heinicke T, Schroll S, Larsen TS, Thurner L, Pukrop T, Salwender H, Naumann R, Hess G, Kroschinsky FP, Blystad AK, Keller U, Pulczynski EJ, Pedersen MB, Re F, Orsucci L, Pospiech L, La Rosee P, Deckert M, Ponzoni M, Gmehlin D, Backenstrass M, Jensch A, Valk E, Calimeri T, Kasenda B, Trepel M, Fricker H, Semenova I, Scherer F, von Gottberg P, Burger E, Grishina O, Hader C, Ihorst G, Finke J, Zucca E, Schorb E. High-dose chemotherapy followed by autologous stem-cell transplantation versus non-myeloablative consolidation in primary CNS lymphoma (MATRix/IELSG43): a randomised phase 3 trial. Lancet. 2026 Aug 8;408(10554):532-544. doi: 10.1016/S0140-6736(26)00917-7. Epub 2026 Jul 22.
- Derived from this study: PubMed 27098429Schorb E, Finke J, Ferreri AJ, Ihorst G, Mikesch K, Kasenda B, Fritsch K, Fricker H, Burger E, Grishina O, Valk E, Zucca E, Illerhaus G. High-dose chemotherapy and autologous stem cell transplant compared with conventional chemotherapy for consolidation in newly diagnosed primary CNS lymphoma--a randomized phase III trial (MATRix). BMC Cancer. 2016 Apr 21;16:282. doi: 10.1186/s12885-016-2311-4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerald Illerhaus, PhD principal investigator
Representative of Sponsor
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®) and Arm B (TEPADINA®-CARMUBRIS®-Busilvex®) in people with Diffuse Large B-cell-lymphoma, run by University Hospital Freiburg at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elisabeth Schorb, PhD (0049761270 ext. 33210, elisabeth.schorb@uniklinik-freiburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measure PFS will be measured by the number of events (PD, relapse or death from any cause) within the treatment arms (time frame: PFS is defined as the time from randomization until PD or relapse or death from any cause up to 24 months after end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02531841, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2015.