Safety and Feasibility Study for CNS-Relapse Prevention in High-Risk Diffuse Large B-cell Lymphoma With Thiotepa-based Autologous Stem Cell Transplant (CNS-PHLAT)

Summary

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.

Eligibility

Age range

18–75 years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  Thiotepa

  Thiotepa will be given intravenously twice daily on Days -5 and -4 over 120 minutes at a dose of 5 mg/kg.

• Drug
  Carmustine

  Carmustine will be given intravenously on Day -6 over 120 minutes at a dose of 400 mg/m\^2.

• Procedure
  Autologous Stem Cell Transplant

  Infusion of autologous peripheral blood stem cells on Day 0.

• Drug
  Anthracycline-based induction chemotherapy

  Standard of care, not dictated by protocol.

Location