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High-dose Chemotherapy with Thiotepa, Busulfan, and Cyclophosphamide Followed by Autologous Stem Cell Transplantation in Central Nervous System Lymphoma

NCT06625359 · Status: TERMINATED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 17

Last updated 2024-10-03

No results posted yet for this study

Summary

The involvement of the central nervous system (CNS) by non-Hodgkin lymphoma (NHL) has carried a poor prognosis. For both of primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), high-dose methotrexate (HD- MTX) based chemotherapy and combined modality have significantly improved the previously poor response rates and prognosis. However, in PCNSL, relapse rates have remained high, with only 20% to 30% patients achieving a durable long-term remission after HD-MTX. The combination with whole-brain radiotherapy (WBRT) has resulted in higher disease-free and overall survival rates, but it has also been associated with severe neurotoxicity. Patients with SCNSL fare the worst, typically succumbing to disease within median 2.5 to 4 months with 1-year survival rates of only 25%.

Because of these dismal outcomes, intensification of the high-dose chemotherapy (HDC)with autologous stem cell transplantation (autoSCT) has been explored for PCNSL and SCNSL as salvage treatment in patients with refractory or relapsed disease, and as consolidation after primary chemotherapy, replacing or preceding WBRT. Thiotepa, busulfan, and cyclophosphamide (TBC) have significant penetration of blood-brain barrier as shown in several pharmacokinetic studies. Thus, combination of these 3 agents was proposed as one high-dose chemotherapy regimen to achieve therapeutic concentrations in the lymphoma tissue in chemotherapy sanctuaries, like cerebrospinal fluid (CSF), meninges and eyes. eyes. Several studies have shown promising results and favorable long-term toxicity profiles with this combination. However, the relatively rarity of this tumor precludes rapid completion of large-scale phase III trial and, therefore, our reliance on the results of well-designed phase II trials is critical. Therefore, we evaluate the efficacy and toxicity of thiotepa, bulsulfan, and cyclophosphamide as a conditioning for autologous stem cell transplantation in patients with PCNSL and SCNSL.

Conditions

  • Central Nervous System Lymphoma

Interventions

DRUG

Thiotepa in conditioning before transplantation

For patients with ECOG PS 0 or 1 For patients with ECOG PS 0 or 1 and age \< 60 years old, conditioning regimen before autologous stem cell transplantation consists of thiotepa, bulsulfan, and cyclophosphamide from day -9. Beginning on day -9 and through day -7, each patient was treated with thiotepa (200mg/m m2 IV per day). On days -6 to -4, patients received bulsulfan (2.7mg/kg IV over 3 hours per day every). Bulsulfan-related seizure prophylaxis was given with levetriacetam (1500mg loading on day -6, 500mg twice daily on days -5 to -3). On days -3 and -2, cyclophosphamide (60mg/kg IV per day) was given given. Patients with ECOG PS 2 or age ≥ 60 years old received bulsulfan (3.2mg/kg IV over 3 hours per day for 2 days) resulting in 8 days regimen.

Sponsors & Collaborators

  • Seoul National University Hospital

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
19 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-06-01
Primary Completion
2024-09-30
Completion
2024-09-30

Countries

  • South Korea

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06625359 on ClinicalTrials.gov