Clinical trial NCT06687772: CNS-Relapse Prevention in High-Risk Diffuse Large B-cell Lymphoma With Thiotepa-based Autologous Stem Cell Transplant
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Keywords: Diffuse large B-cell lymphoma
Autologous stem cell transplant
CNS lymphoma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2024-11-14
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Feasibility of treatment
timeFrame: Through completion of treatment (estimated to be 6 months)
Secondary outcomes:
measure: Rate of selected transplant-related grade 3-5 adverse events
timeFrame: From start of study treatment through day 30 after transplant (estimated to be 7 months)
measure: Rate of CNS relapse
timeFrame: At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)
measure: Progression-free survival (PFS)
timeFrame: At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)
measure: Overall survival (OS)
timeFrame: At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)
measure: Non-relapse mortality
timeFrame: At 2 years post-thiotepa/carmustine conditioning and ASCT (estimated to be 2.5 years)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Amanda F Cashen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: