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Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by International Extranodal Lymphoma Study Group (IELSG)
Sponsor:
Information provided by (Responsible Party):
International Extranodal Lymphoma Study Group (IELSG)
ClinicalTrials.gov Identifier:
NCT01011920
First received: November 9, 2009
Last updated: November 22, 2013
Last verified: March 2013

November 9, 2009
November 22, 2013
November 2009
December 2013   (final data collection date for primary outcome measure)
response rate after primary chemotherapy and 2 years failure free survival at second randomization [ Time Frame: 3 months, 2 years ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01011920 on ClinicalTrials.gov Archive Site
  • safety, as acute and long-term toxicity [ Time Frame: Throughout all the active treatment period ] [ Designated as safety issue: Yes ]
  • overall survival [ Time Frame: From entry onto trial until death for any cause ] [ Designated as safety issue: No ]
  • safety, as acute and long-term toxicity
  • overall survival
Not Provided
Not Provided
 
Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma
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

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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Central Nervous System Lymphoma
  • Drug: Methotrexate
    Methotrexate 3.5 g/m2 (0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion) on day 1, every 3 weeks for a maximum of 4 courses.
  • Drug: Ara-C
    Cytarabine 2 g/m2 (1 hr infusion, twice a day every 12 hours), on d 2 - 3 every 3 weeks for a maximum of 4 courses
    Other Name: Cytarabine
  • Drug: Rituximab
    Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
    Other Name: MabThera
  • Drug: Thiotepa
    ARM C: Thiotepa 30 mg/m2 (30 min. Infusion) on day 4 every 3 weeks for a maximum of 4 courses ARM E: Thiotepa 5 mg/kg in 250 ml saline sol 2-hr inf. every 12 hrs days -5 & -4
  • Radiation: radiotherapy
    Photons of 4-10 Mev, 180 cGy per day, 5 weekly fractions. Whole-brain will be irradiated by two opposite lateral fields including the first two cervical vertebras and the posterior two thirds of the orbits, which must be shielded after 30 Gy (after 36 Gy in the case of evident intraocular disease at diagnosis). Tumor-bed (boost or partial-brain RT) will be irradiated by 2 to 4 isocentric treatment fields based on tumor location, with all portals treated per each RT session.
  • Drug: BCNU
    BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6
    Other Name: Carmustine
  • Other: APBSCT
    Autologous peripheral blood stem cell transplant (APBSCT)
  • Experimental: MTX+ AraC
    Arm A 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
    Interventions:
    • Drug: Methotrexate
    • Drug: Ara-C
  • Experimental: Ara-C +Rituximab
    Arm B 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
    Interventions:
    • Drug: Ara-C
    • Drug: Rituximab
  • Experimental: Ara-C + rituximab+thiotepa
    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
    Interventions:
    • Drug: Ara-C
    • Drug: Rituximab
    • Drug: Thiotepa
  • Experimental: WBRT 36 Gy +/- boost 9 Gy
    ARM D: WBRT with 36 Gy in the case of CR to primary chemotherapy or the same WBRT dose followed by a tumor-bed boost of 9 Gy with 1-2 cm of margin surrounding enhanced residual lesion (total tumor-bed dose 45 Gy) in patients who achieved a PR or SD after primary chemotherapy. Photons of 4-10 Mev, 180 cGy per day, 5 weekly fractions.
    Intervention: Radiation: radiotherapy
  • Experimental: BCNU + Thiotepa + APBSCT
    Arm E BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6 Thiotepa 5 mg/kg in 250 ml saline sol 2-hr inf. every 12 hrs days -5 & -4 Reinfusion of PBSC ≥5 x 106 CD34+ cells/kg day 0
    Interventions:
    • Drug: Thiotepa
    • Drug: BCNU
    • Other: APBSCT
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
126
December 2016
December 2013   (final data collection date for primary outcome measure)

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.

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.
  • Concurrent treatment with other experimental drugs.
  • Concurrent Pregnancy or lactation.
  • Patients not agreeing to take adequate contraceptive measures during the 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).
Both
18 Years to 65 Years
No
Contact: Emanuele Zucca, MD ++41918119040 ielsg@ticino.com
Germany,   Italy,   Switzerland,   United Kingdom
 
NCT01011920
IELSG32
Yes
International Extranodal Lymphoma Study Group (IELSG)
International Extranodal Lymphoma Study Group (IELSG)
Not Provided
Study Chair: Andrés JM Ferreri, MD San Raffaele H Scientific Institute, Milan, Italy
Study Chair: Gerald Illerhaus, MD University Medical Center, Freiburg, Germany
Principal Investigator: Emanuele Zucca, MD IOSI, Bellinzona, Switzerland
International Extranodal Lymphoma Study Group (IELSG)
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP