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High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma (MATRix)

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ClinicalTrials.gov Identifier: NCT02531841
Recruitment Status : Recruiting
First Posted : August 25, 2015
Last Update Posted : August 25, 2015
Sponsor:
Collaborators:
German Federal Ministry of Education and Research
International Extranodal Lymphoma Study Group (IELSG)
Information provided by (Responsible Party):
Elisabeth Schorb, University Hospital Freiburg

Brief 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 cycles of conventional chemotherapy with R-DeVIC (rituximab, dexamethasone, etoposide, ifosfamide, carboplatin).

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell-lymphoma Drug: Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®) Drug: Arm B (TEPADINA®-CARMUBRIS®-Busilvex®) Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High-dose Chemotherapy and Autologous Stem Cell Transplant or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma - Randomized Phase III Trial
Study Start Date : July 2014
Estimated Primary Completion Date : November 2017
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Active Comparator: Arm A

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)
Drug: Arm A (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)
Other Name: Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®
Active Comparator: Arm B

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)
Drug: Arm B (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)
Other Name: TEPADINA®-CARMUBRIS®-Busilvex®



Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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 ]
    Response will be measured by the IPCG response criteria.

  2. 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 ]

    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


  3. 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 ]

    Timepoints of evaluation are defined as every assessment during follow up period in accordance with the protocol.

    year 1-2: every 3 month


  4. 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. ]
    After this time period, only SAEs judged by the investigator to be related to at least one of investigational products will be reported

  5. 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. ]
    If an abnormal parameter is not listed in the toxicity table, an AE must be documented

  6. 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. ]
    Timepoints of evaluation are defined as every assessment during follow up period in accordance with the protocol



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Immunocompetent patients with newly-diagnosed primary central nervous system B-cell lymphoma
  2. Age 18-65 years irrespective of ECOG or 66-70 years (with ECOG Performance Status ≤2)
  3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist.
  4. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
  5. Disease exclusively located in the CNS
  6. At least one measurable lesion
  7. Previously untreated patients (previous or ongoing steroid treatment admitted)
  8. Sexually active patients of childbearing potential who agree to take adequate contraceptive measures during study participation
  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. Sufficient stem cell harvest (≥ 5 x 106 CD34+ cells/kg of body weight)
  2. Complete remission, unconfirmed complete remission or partial remission
  3. Central pathology results confirming local results

Exclusion Criteria:

  1. Congenital or acquired immunodeficiency
  2. Systemic lymphoma manifestation (outside the CNS)
  3. Isolated ocular lymphoma without manifestation in the brain parenchyma or spinal cord
  4. 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
  5. Previous Non-Hodgkin lymphoma at any time
  6. 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)
  7. HBsAg, anti-HBc or HCV positivity
  8. HIV infection, previous organ transplantation or other clinical evident form of immunodeficiency
  9. Concurrent treatment with other experimental drugs or participation in a clinical trial within the last thirty days before the start of this study
  10. 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)
  11. Severe non-compensated pulmonary disease (IVC <55%, DLCO <40%)
  12. Third space fluid accumulation >500 ml
  13. Hypersensitivity to study treatment or any component of the formulation
  14. Taking any medications likely to cause interactions with the study medication
  15. Known or persistent abuse of medication, drugs or alcohol
  16. Patient without legal capacity and who is unable to understand the nature, significance and consequences of the study and without designated legal representative
  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. Concurrent (or planned) pregnancy or lactation
  20. Fertile patients refusing to use safe contraceptive methods during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02531841


Contacts
Contact: Elisabeth Schorb, PhD 0049761270 ext 33210 elisabeth.schorb@uniklinik-freiburg.de
Contact: Elvira Burger 0049761270 ext 73780 elvira.burger@uniklinik-freiburg.de

Locations
Germany
University Hospital Freiburg - Department for Hematology, Oncology and Stem cell Transplantion Recruiting
Freiburg, Baden-Wuerttemberg, Germany, 79106
Contact: Juergen Finke, PhD    +49761270 ext 34080    juergen.finke@uniklinik-freiburg.de   
Contact: Elisabeth Schorb, PhD    +49761270 ext 33210    elisabeth.schorb@uniklinik-freiburg.de   
Klinikum Stuttgart, Clinic of Hematology, Oncology and Palliative Care, Stuttgart Cancer Center / Tumor Center Eva Mayr-Stihl Recruiting
Stuttgart, Baden-Wuerttemberg, Germany, 70174
Contact: Gerald Illerhaus, PhD    +49 711 278 ext 30400    G.Illerhaus@klinikum-stuttgart.de   
Contact: Kristina Mikesch, PhD    +49 711 278 ext 30403    k.mikesch@klinikum-stuttgart.de   
Sponsors and Collaborators
University Hospital Freiburg
German Federal Ministry of Education and Research
International Extranodal Lymphoma Study Group (IELSG)
Investigators
Principal Investigator: Gerald Illerhaus, PhD Representative of Sponsor

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Elisabeth Schorb, Medical Trial Coordinator, University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT02531841     History of Changes
Other Study ID Numbers: DRKS00005503
First Posted: August 25, 2015    Key Record Dates
Last Update Posted: August 25, 2015
Last Verified: August 2015

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Etoposide phosphate
Isophosphamide mustard
Rituximab
Methotrexate
Cytarabine
Busulfan
Thiotepa
Carmustine
Etoposide
Dexamethasone
Ifosfamide
BB 1101
Dexamethasone acetate
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents