A serious consequence of systemic diffuse large B-cell lymphoma (DLBCL) is secondary central nervous system (CNS) relapse, which occurs in approximately 5% of all patients. Many CNS relapses occur within the first year after completion of frontline treatment and are associated with significantly increased mortality; thus, it is important to tailor frontline treatment to provide prophylaxis against CNS relapse in those patients who are determined to be high-risk.
Autologous stem cell transplantation (ASCT) is standard of care for patients with DLBCL who relapse one year or more after first remission, and it has been shown to improve progression-free survival for patients with primary CNS lymphoma.
The four-drug BEAM regimen (carmustine, etoposide, cytarabine, and melphalan) is the preferred conditioning regimen for DLBCL patients undergoing ASCT; however, patients with primary CNS lymphoma receive thiotepa plus carmustine as their conditioning regimen due to its better CNS penetration.
This study tests the hypothesis that consolidation thiotepa/carmustine ASCT in first complete remission will reduce the risk of CNS relapse in transplant-eligible patients with DLBCL with no prior CNS disease at high risk of secondary CNS recurrence.
Newly diagnosed diffuse large B-cell lymphoma, large B-cell lymphoma transformed from underlying indolent lymphoma, or high-grade B-cell lymphoma. Patients with secondary CNS lymphoma are eligible. Patients with Richter's transformation are NOT eligible.
CNS-IPI ≥ 4
Kidney or adrenal involvement
Testicular involvement
Relapsed or refractory diffuse large B-cell lymphoma or high-grade B-cell lymphoma. Prior treatment for underlying indolent lymphoma is permitted.
Diagnosis of primary CNS lymphoma.
Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen as determined by the PI. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
Currently receiving any other investigational agents.
Single group
Thiotepa
DrugThiotepa will be given intravenously twice daily on Days -5 and -4 over 120 minutes at a dose of 5 mg/kg.
Carmustine
DrugCarmustine will be given intravenously on Day -6 over 120 minutes at a dose of 400 mg/m\^2.
Autologous Stem Cell Transplant
Procedure/SurgeryInfusion of autologous peripheral blood stem cells on Day 0.
Anthracycline-based induction chemotherapy
DrugStandard of care, not dictated by protocol.
Feasibility of treatment
\- The treatment (thiotepa/carmustine conditioning and ASCT) will be considered feasible if \> 50% of enrolled patients meet the following criteria: * Achieve CR at the end of induction chemotherapy * Remain eligible for ASCT * Collect sufficient stem cells for ASCT (CD34+ cell goal ≥2 x 10\^6/kg) * Complete thiotepa/carmustine chemotherapy and undergo ASCT
Rate of selected transplant-related grade 3-5 adverse events
Rate of CNS relapse
Progression-free survival (PFS)
Overall survival (OS)
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