High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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, dexamethasone, etoposide, ifosfamide, carboplatin).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Freiburg
• Collaborators: German Federal Ministry of Education and Research; International Extranodal Lymphoma Study Group (IELSG)
• Treatments: BB 1101; Busulfan; Carmustine; Cytarabine; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Methotrexate; Rituximab; Thiotepa

Criteria

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.

4. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy

5. Disease exclusively located in the CNS

6. At least one measurable lesion

7. Previously untreated patients (previous or ongoing steroid treatment admitted)

8. Sexually active patients of childbearing potential who agree to take adequate contraceptive measures during study participation

9. 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

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. 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 or 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