CNS-Relapse Prevention in High-Risk Diffuse Large B-cell Lymphoma With Thiotepa-based Autologous Stem Cell Transplant
- Conditions
- Interventions
- Registration Number
- NCT06687772
- Lead Sponsor
- Washington University School of Medicine
- 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 ...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 36
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Newly diagnosed diffuse large B-cell lymphoma, large B-cell lymphoma transformed from underlying indolent lymphoma, or high-grade B-cell lymphoma.
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At high risk for CNS relapse as defined by at least one of the criteria below:
- CNS-IPI ≥ 4
- Kidney or adrenal involvement
- Testicular involvement
- Double hit lymphoma as defined by containing translocations of MYC gene together with rearrangement of BCL2 and/or BCL6.
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Will receive a full course (6 cycles) 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.
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Eligible for autologous stem cell transplant as determined by the treating physician.
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Ages 18 to 75.
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ECOG performance status ≤ 2.
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Thiotepa and carmustine can cause fetal harm when administered to a pregnant person. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after completion of study participation (for women) and 12 months after completion of study participation (for men). Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform the treating physician immediately.
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Ability to understand and willingness to sign an IRB-approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants if patient is otherwise unable to sign for themselves or unable to understand consent document
- Relapsed or refractory diffuse large B-cell lymphoma or high-grade B-cell lymphoma.
- Diagnosis of primary CNS lymphoma.
- Diagnosis of secondary CNS involvement at baseline.
- 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 of study entry.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine Thiotepa * Patients should receive induction treatment with anthracycline-based chemotherapy regimen per standard of care (6 cycles). Management, dose delays, and dose modifications will be per standard of care and treating physician discretion; administration of anthracycline-based induction therapy is not dictated by the study. Patients who have a PR by PET criteria but whose residual abnormality on PET is unlikely to represent residual disease may proceed to ASCT. * After confirmation of 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. Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine Carmustine * Patients should receive induction treatment with anthracycline-based chemotherapy regimen per standard of care (6 cycles). Management, dose delays, and dose modifications will be per standard of care and treating physician discretion; administration of anthracycline-based induction therapy is not dictated by the study. Patients who have a PR by PET criteria but whose residual abnormality on PET is unlikely to represent residual disease may proceed to ASCT. * After confirmation of 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. Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine Autologous Stem Cell Transplant * Patients should receive induction treatment with anthracycline-based chemotherapy regimen per standard of care (6 cycles). Management, dose delays, and dose modifications will be per standard of care and treating physician discretion; administration of anthracycline-based induction therapy is not dictated by the study. Patients who have a PR by PET criteria but whose residual abnormality on PET is unlikely to represent residual disease may proceed to ASCT. * After confirmation of 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. Anthracycline-based induction chemotherapy + ASCT + Thiotepa + Carmustine Anthracycline-based induction chemotherapy * Patients should receive induction treatment with anthracycline-based chemotherapy regimen per standard of care (6 cycles). Management, dose delays, and dose modifications will be per standard of care and treating physician discretion; administration of anthracycline-based induction therapy is not dictated by the study. Patients who have a PR by PET criteria but whose residual abnormality on PET is unlikely to represent residual disease may proceed to ASCT. * After confirmation of 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.
- Primary Outcome Measures
Name Time Method Feasibility of treatment Through completion of treatment (estimated to be 6 months) - 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)
...
- Secondary Outcome Measures
Name Time Method 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)
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States