Trial document




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  DRKS00003763

Trial Description

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Title

Randomized Phase II Trial On Primary Chemotherapy With High-Dose Methotrexate And High-Dose Cytarabine With Or Without Thiotepa, And With Or Without Rituximab, Followed By Brain Irradiation Vs. High-Dose Chemotherapy Supported By Autologous Stem Cells Transplantation For Immunocompetent Patients With Newly Diagnosed Primary CNS Lymphoma

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Trial Acronym

Freiburger IELSG PCNSL-Studie

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URL of the Trial

[---]*

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Brief Summary in Lay Language

This is a multicenter open label randomized phase II trial.

Enrolled Primary Central Nervous System Lymphoma (PCNSL) patients will be stratified
according to the IELSG score and randomized to receive one of the follows as primary
chemotherapy:

- Arm A: Methotrexate (MTX) + Cytarabine (Ara-C)

- Arm B: MTX + Ara-C + rituximab

- Arm C: MTX + Ara-C + rituximab + thiotepa.

Chemotherapy will be administered every three weeks. The maximum number of chemotherapy
induction courses will be 4. Patients in Stable Disease (SD) or better after two courses
will receive two more courses of the same primary chemotherapy regimen. Stem-cells harvest
will be performed in the three arms after the second course. After 4 courses response
assessment will be performed.

Patients who will not achieve SD or better after the 4th course, as well as those who will
experience Progressive Disease (PD) at any time and those who will not achieve a sufficient
stem cell harvest, will receive Whole Brain Radiation Therapy (WBRT) 36-40 Gy +/- tumor bed
boost of 9 Gy.

Patients who will achieve SD or better after the 4th course will be stratified according to
objective response to primary chemotherapy and to primary chemotherapy regimen and
randomly allocated to receive as consolidation therapy one of the follows:

- Arm D: WBRT 36 Gy +/- boost 9 Gy

- Arm E: Carmustine (BCNU) + Thiotepa + Autologous Peripheral Blood Stem Cell Transplant
(APBSCT) Patients in Complete Response (CR) after WBRT or APBSCT will remain in
follow-up. Patients who will not achieve a CR after WBRT will be managed according to
physician's preferences. Patients who will not achieve a CR after APBSCT will be
referred to WBRT.

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Brief Summary in Scientific Language

The primary endpoint of the study at first randomization is to establish in a prospective, randomized phase II trial, the activity of three different chemotherapy combinations with high-dose methotrexate (HD-MTX) + high-dose cytarabine (HD-araC), HD-MTX + HD-araC + rituximab and HD-MTX + HD-araC + rituximab + thiotepa in patients with newly diagnosed PCNSL.

The primary endpoint of the study at second randomization is to establish in a prospective, randomized phase II trial, the efficacy of two consolidation strategies: conventional whole-brain radiotherapy (WBRT) vs. high-dose chemotherapy supported by autologous stem cell transplantation (HDC + ASCT) in patients with newly diagnosed PCNSL.

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Do you plan to share individual participant data with other researchers?

[---]*

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00003763
  •   2012/05/08
  •   2009/11/09
  •   yes
  •   Approved
  •   121/10, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   2009-012432-32 
  •   NCT01011920  (ClinicalTrials.gov)
  •   4036295 
  •   IELSG32  (International Extranodal Lymphoma Study Group (IELSG))
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Health Condition or Problem studied

  •   Central Nervous System Lymphoma
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Interventions/Observational Groups

  •   Arm A (cycle 1 and 2)
    Methotrexate 3.5 g/m2 0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion d 1
    Cytarabine 2 g/m2 1 hr infusion, twice a day (every 12 hs.) d 2 - 3
  •   Arm B (cycle 1 and 2)
    Rituximab 375 mg/m2 conventional infusion d -5 & 0
    Methotrexate 3.5 g/m2 0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion d 1
    Cytarabine 2 g/m2 1 hr infusion, twice a day (every 12 hs.) d 2 - 3

  •   Arm C
    Rituximab 375 mg/m2 conventional infusion d -5 & 0
    Methotrexate 3.5 g/m2 0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion d 1
    Cytarabine 2 g/m2 1 hr infusion, twice a day (every 12 hs.) d 2 - 3
    Thiotepa 30 mg/m2 30 min. Infusion d 4
  •   Staging - after cycle 2 and 4: MRT, CSF puncture (when CSF is affected, further check only if result ist positive) CR, PR, SD: continuation of chemotherapy with cycle 3 and 4 PD or unsufficent stem cell harvest: WBRT 36-40 Gy +/- tumor bed boost with 9 Gy
  •   Harvest: only cycle 2
    from day 6: Filgrastim
    app. on day 10: Leukapheresis

    -> Consolidation Therapy

  •   Arm D
    - CR : WBRT 36 Gy
    PR, SD: WBRT 36-40 Gy +/- Tumor-bed Boost mit 9 Gy
  •   Arm E
    day -6: BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf.

    days -5 & -4 Thiotepa 2 * 5 mg/kg in 250 ml saline sol 2-hr inf. every 12 hrs

    day 0: Reinfusion of PBSC 5 x 10exp 6 CD34+ cells/kg

    from day 6 on: Filgrastim
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   II
  •   [---]*
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Primary Outcome

- response rate after primary chemotherapy and 2 years failure free survival at second randomization; time frame: 3 months, 2 years

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Secondary Outcome

- safety, as acute and long-term toxicity
- overall survival

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Countries of Recruitment

  •   Germany
  •   Italy
  •   Switzerland
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Locations of Recruitment

  •  
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  •  
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2010/09/28
  •   227
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   65   Years
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Additional Inclusion Criteria

- Histological or cytological assessed diagnosis of non-Hodgkin's lymphoma.

- Diagnostic sample obtained by stereotactic or surgical biopsy, Cerebrospinal Fluid
(CSF) cytology examination or vitrectomy.

- Disease exclusively localized into the central nervous system, CSF, cranial nerves or
eyes.

- At least one measurable lesion.

- Previously untreated patients (previous or ongoing steroid therapy admitted).

- Age 18-65 years (with ECOG Performance Status 0-3) or 66-70 (with ECOG Performance
Status 0-2).

- Adequate bone marrow, renal, cardiac, and hepatic function.

- Sexually active patients of childbearing potential agreeing in implementing adequate
contraceptive measures during study participation.

- Absence of any familial, sociological or geographical condition potentially hampering
compliance with the study protocol and follow-up schedule.

- Patient-signed informed consent obtained before registration.

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Exclusion Criteria

- Patients with lymphomatous lesions outside the CNS.

- Patients with a previous non-Hodgkin lymphoma at any time.

- Previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other cancers without evidence of
disease at least from 5 years.

- HBsAg and HCV positivity.

- HIV infection, previous organ transplantation or other clinically evident form of immunodeficiency.

- Patients with the following hematological parameters: Hb< 9g/dl, Neutrophils< 2.000/µl, Thrombocytes< 100.000/µl
Creatinine clearance < 60ml/min
Bilirubin > 3mg/dl, AST/ALT and yGT ≥ 2x increased over normal value

- cardial ejection fraction < 50%; 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)

- Concurrent treatment with other experimental drugs.

- Concurrent Pregnancy or lactation.

- Patients not agreeing to take adequate contraceptive measures during the study.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Freiburg, Abt. Med 1, Hämatologie/ Onkologie
    • Mr.  Prof. Dr. med.  Gerald  Illerhaus 
    • Hugstetter Strasse 55
    • 79106  Freiburg
    • Germany
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    • Universtitätsklinikum Freiburg
    • Mr.  Prof. Dr. med.  Gerald  Illerhaus 
    • Hugstetter Strasse 555
    • 79106  Freiburg
    • Germany
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    • Universitätsklinikum Freiburg
    • Mr.  Prof. Dr. med.  Gerald  Illerhaus 
    • Hugstetter Strasse 55
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum Freiburg Abt. Medizinische Klinik I Hämatologie/ Onkologie
    • Mr.  Prof. Dr. med.  Gerald  Illerhaus 
    • Hugstetter Strasse 55
    • 79106  Freiburg
    • Germany
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.