Clinical trial NCT01011920: Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Central Nervous System Lymphoma
Keywords: newly diagnosed primary central nervous system lymphoma
Lead sponsor: International Extranodal Lymphoma Study Group (IELSG)
Sponsor class: OTHER
First posted: 2009-11-11
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: response rate after primary chemotherapy and 2 years failure free survival at second randomization
timeFrame: 3 months, 2 years
Secondary outcomes:
measure: safety, as acute and long-term toxicity
timeFrame: Throughout all the active treatment period
measure: overall survival
timeFrame: From entry onto trial until death for any cause
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: "Klinik für Hämatologie Universitätsklinikum Essen"
city: Freiburg
country: Germany
facility: Uniklinik Freiburg
city: Hamburg
country: Germany
facility: Universitätskrankenhaus Hamburg-Eppendorf
city: Jena
country: Germany
facility: Friedrich Schiller Universitaet Jena
city: Mainz
country: Germany
facility: Johannes Gutenberg Universität Mainz
city: München
country: Germany
facility: Technische Universität in München
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e Cesare Arrigo
city: Brescia
country: Italy
facility: Spedali Civili
city: Milan
country: Italy
facility: San Raffaele H Scientific Institute
city: Nocera Inferiore
country: Italy
facility: Ospedale Umberto I
city: Pescara
country: Italy
facility: Ospedale Civile S.Spirito
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Istituto Nazionale dei Tumori Regina Elena
city: Roma
country: Italy
facility: Università degli Studi La Sapienza
city: Rozzano
country: Italy
facility: Humanitas
city: Torino
country: Italy
facility: Ospedale Maggiore S. Giovanni Battista
city: Verona
country: Italy
facility: Policlinico G.B. Rossi
city: Bellinzona
country: Switzerland
facility: IOSI - Oncology Institute of Southern Switzerland
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Romford
country: United Kingdom
facility: Queen's Hospital
Study officials:
affiliation: San Raffaele H Scientific Institute, Milan, Italy
name: Andrés JM Ferreri, MD
role: STUDY_CHAIR
affiliation: University Medical Center, Freiburg, Germany
name: Gerald Illerhaus, MD
role: STUDY_CHAIR
affiliation: IOSI, Bellinzona, Switzerland
name: Emanuele Zucca, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosee P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sonderskov Gorlov J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG). Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017 Nov;4(11):e510-e523. doi: 10.1016/S2352-3026(17)30174-6. Epub 2017 Oct 17.
citation: Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosee PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Ruda R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gorlov JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG). Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. doi: 10.1016/S2352-3026(16)00036-3. Epub 2016 Apr 6.