CNS-Relapse Prevention in High-Risk Diffuse Large B-cell Lymphoma With Thiotepa-based Autologous Stem Cell Transplant

NCT06687772 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202411136
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Diffuse large B-cell lymphoma; Autologous stem cell transplant; CNS lymphoma

Outcome Measures

Primary Outcomes (1)

• 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

  Through completion of treatment (estimated to be 6 months)

Secondary Outcomes (5)

• Rate of selected transplant-related grade 3-5 adverse events

  From start of study treatment through day 30 after transplant (estimated to be 7 months)

• Rate of CNS relapse

  At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)

• Progression-free survival (PFS)

  At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)

• Overall survival (OS)

  At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)

• Non-relapse mortality

  At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)

Study Arms (1)

Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine

EXPERIMENTAL

* Patients should receive induction treatment with anthracycline-based chemotherapy regimen per standard of care. Between the end of induction Cycle #2 and the end of induction Cycle #4, a PET/CT scan should be performed to assess response. If there are no signs of progressive disease and the treating physician recommends patient is eligible for ASCT, patients should be consented with the treatment consent. Treatment with thiotepa and carmustine may not take place prior to this second patient consent. Within 3 weeks after the end of the final cycle of induction, a PET-/CT scan should be performed to assessconfirm treatment response and eligibility for ASCT. * After signing the treatment consent and confirming complete response (CR) following induction therapy, patients will begin conditioning with thiotepa (days -5 and -4) and carmustine (day -6), followed by ASCT on day 0.

Drug: Thiotepa; Drug: Carmustine; Procedure: Autologous Stem Cell Transplant; Drug: Anthracycline-based induction chemotherapy

Interventions

Thiotepa DRUG

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

Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine

Carmustine DRUG

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

Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine

Autologous Stem Cell Transplant PROCEDURE

Infusion of autologous peripheral blood stem cells on Day 0.

Also known as: ASCT

Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine

Anthracycline-based induction chemotherapy DRUG

Standard of care, not dictated by protocol.

Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• At high risk for CNS relapse prior to start of induction as defined by at least one of the criteria below:
• CNS-IPI ≥ 4
• Kidney or adrenal involvement
• Testicular involvement
• Breast involvement
• Ovarian involvement
• Uterine involvement
• Skin involvement
• Double hit lymphoma as defined by containing translocations of MYC gene together with rearrangement of BCL2 and/or BCL6.
• Bone marrow involvement
• Myocardium involvement
• CNS adjacent
• Secondary CNS involvement
• Intend to receive a full course of curative-intent anthracycline-based induction treatment and has not yet received more than 2 cycles at the time of screening. Can receive induction chemotherapy outside of Siteman if still compliant with study eligibility, laboratory studies, lumbar punctures, imaging, and other events.

You may not qualify if:

• 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.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to thiotepa, carmustine, or other agents used in the study.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days prior to start of induction (for people enrolling prior to induction) or within 7 days of enrollment (for people enrolling after the start of induction).

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Thiotepa; Carmustine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds

Study Officials

• Amanda F Cashen, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amanda F Cashen, M.D.

CONTACT

314-454-8306; acashen@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2024
• First Posted: November 14, 2024
• Study Start: January 16, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)