Early Systemic Central Nervous System Prophylaxis in Diffuse Large B-cell Lymphoma

This is a prospective phase 2 clinical trial of systemic central nervous system prophylaxis
among patients with diffuse large B-cell lymphoma at high risk of central nervous system
recurrence. The main objective is to evaluate safety and efficacy of early institution of
intensive central nervous system prophylaxis in a high-risk group to minimize the risk of a
devastating central nervous system recurrence. Patients receive standard primary
immunochemotherapy with an addition of planned central nervous system prophylaxis courses on
or around day 15 of cycles 2, 4, and 6. Growth factor support and Pneumocystis jirovecii
prophylaxis is required. The primary endpoint of this pilot study is protocol-defined
toxicity, whereas efficacy (cumulative incidence of central nervous system recurrence) will
be a secondary endpoint.

Inclusion Criteria:

- New diagnosis of diffuse large B-cell lymphoma, planned first-line therapy using the
standard rituximab- and anthracycline-containing regimens

- No central nervous system involvement on initial staging

- Performance status of 0 or 1 (Eastern Cooperative Oncology Group scale)

- Renal function: creatinine clearance >45 ml/min

- Not pregnant; agreeable to contraception

- Written informed consent

- High risk for central nervous system recurrence as determined by one of the following
high-risk features:

1. high central nervous system International Prognostic Index,

2. testicular, breast, or uterine involvement,

3. dual expresser or double/triple-hit status,

4. HIV positive status, or

5. Molecularly defined high-risk subtype.

Exclusion Criteria:

- pregancy

- unable to provide informed consent

- significant comorbidity in the investigator's judgement