High-dose chemotherapy and autologous stem cell transplant or consolidating conventional chemotherapy in primary CNS lymphoma -randomized phase III trial
- 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 Bcell origin, accounting to the subtype diffuse large B-cell lymphoma.(DLBCL). Prognosis without treatment resembles that of systemic highgrade NHL, and the median survival of untreated patients with PCNSL is approximately 3 months.MedDRA version: 21.0Level: PTClassification code 10007953Term: Central nervous system lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2012-000620-17-IT
- Lead Sponsor
- CITY OF STUTTGART, REPRESENTED BY KLINIKUM STUTTGART
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 250
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
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 220
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
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 and HCV positivity
8. HIV infection, previous organ transplantation or other clinical evident form of immunodeficiency
9. Concurrent treatment with other experimental drugs or participationin 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 ontraceptive 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
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate the efficacy measured as progression-free survival (PFS)<br>of intensive chemotherapy followed by autologous stem-cell<br>transplantation compared to conventional chemotherapy;Secondary Objective: Confrontare una chemioterapia ad alte dosi seguita da trapianto autologo di cellule staminali o chemioterapia convenzionale ottimizzata in termini di sopravvivenza globale (OS), risposta al trattamento e tossicità da trattamento (neurotossicità ed eventi avversi) in pazienti con PCNSL;Primary end point(s): Progression-free survival (PFS) time from randomization until progression, relapse or death from any cause;Timepoint(s) of evaluation of this end point: Response Assessment III at the end of study treatment (EOT) visit and every imaging diagnostic assessments during follow-up period (for details see protocol intervention scheme, page 19):<br>during year 1-2: every 3 month from year 3-5: every 6 month or imaging in case of clinical suspicion of disease progression or relapse
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Complete response (CR); Response duration; Sopravvivenza globale (OS); Quality of life (QOL): EORTC QLQ-C30; (Serious) adverse events; Toxicity; Neurotoxicity (MMSE, EORTC QLQ-BN20, neuropsychological test<br>battery);Timepoint(s) of evaluation of this end point: day 60 after randomization; ultima visita utile; year 1-2: every 3 month<br>year 3-5: every 6 month; year 1-2: every 3 month year 3-5: every 6 month<br>; year 1-2: every 3 month year 3-5: every 6 month; year 1-2: every 3 month year 3-5: every 6 month; year 1-2: every 3 month year 3-5: every 6 month