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, Dexamthason, Etoposide, Ifosfamide, Carboplatin).

Phase 1

• Conditions: Primary CNS lymphoma (PCNSL) accounts for 1 to 2% of all Non-Hodgkin's lymphomas (NHL) and for 2 to 7% of all primary CNS tumors. It's incidence has increased over the past 30 years, particularly in immunocompetent individuals. Over 90% of PCNSL are lymphomas of B-cell origin, accounting to the subtype diffuse large B-cell lymphoma. (DLBCL). Prognosis without treatment resembles that of systemic high-grade NHL, and the median survival of untreated patients with PCNSL is approximately 3 months.; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2012-000620-17-DE
• Lead Sponsor: andeshauptstadt Stuttgart, represented by the Executive Medical Director Klinikum Stuttgart

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-02-20
• Last Update Posted: 23 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 330

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. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
4.Disease exclusively located in the CNS
5.At least one measurable lesion
6.Previously untreated patients (previous or ongoing steroid treatment admitted)
7.Sexually active patients of childbearing potential who agree to take adequate contraceptive measures during study participation
8.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
4. Exclusion criterion no. 6 not applicable for re-check for randomization

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

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.Only applicable for patient inclusion (registration) not applicable for re-check for randomization: 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 and 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 (for details see clinical trial protocol section 4.3)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified