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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 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.
  • - 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.
  • - 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 (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.
  • - Eligible for autologous stem cell transplant as determined by the treating physician.
  • - Ages 18 to 75.
  • - ECOG performance status ≤ 2.
  • - 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 treatment, and for 6 months following receipt of thiotepa and/or carmustine (for women) and 12 months following receipt of thiotepa and/or carmustine (or 3 months following receipt of carmustine if discontinuing before thiotepa) (for men). Should a woman become pregnant or suspect she is pregnant during treatment or within 6 months of the last dose of either thiotepa or carmustine or should a man suspect he has fathered a child, s/he must inform the treating physician immediately.
  • - 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.

Exclusion Criteria:

  • - 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).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT06687772
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Washington University School of Medicine
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Amanda F Cashen, M.D.
Principal Investigator Affiliation Washington University School of Medicine
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Diffuse Large B Cell Lymphoma
Study Website: View Trial Website
Arms & Interventions

Arms

Experimental: Anthracycline-based induction chemotherapy + ASCT + Thiotepa + 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.

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Washington University School of Medicine, Saint Louis, Missouri

Status

Recruiting

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Site Contact

Amanda F Cashen, M.D.

[email protected]

314-454-8306

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