Clinical trial NCT05831865: Frontline of ASCT in High-risk DLBCL
Official title: The Efficacy and Safety of Autologous Stem Cell Transplantation (ASCT) in Frontline Therapy of Patients With High-Risk Diffuse Large B-Cell Lymphoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diffuse Large B Cell Lymphoma
Keywords: autologous stem cell transplantation
international prognostic index
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
First posted: 2023-04-26
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with DLBCL and an IPI score equal to or greater than three and consent to receive the standard R-CHOP regimen followed by ASCT. During the interim evaluation, patients achieving CR or CMR, will be followed up for up to two years after completing the R-CHOP regimen followed by ASCT. Patients achieving PR or PMR and who are willing to receive Pola-R-CHP as the following treatment regimen followed by ASCT, will also be followed up for up to two years. Patients achieving less than a PR or PMR response will be excluded from the study.

Brief summary: The role of frontline therapy of autologous stem cell transplant (ASCT) in diffuse large B-cell lymphoma (DLBCL) is controversial. The investigators aim to conduct this prospective study to observe the efficacy and safety of ASCT as frontline therapy in DLBCL patients with high-risk disease, defined by an International Prognostic Index (IPI) score equal to or greater than three.

Detailed description: There is evidence to suggest that chemotherapy followed by ASCT may be more effective than standard chemotherapy alone as a frontline treatment for high-risk DLBCL patients. However, the use of ASCT as frontline therapy for DLBCL remains controversial due to concerns over the potential toxicities of the procedure, as well as questions about which patients would benefit most from this approach.

The investigators aim to conduct this prospective study to observe the efficacy and safety of ASCT as frontline therapy in DLBCL patients with high-risk disease, defined by an International Prognostic Index (IPI) score equal to or greater than 3 points.

Patients diagnosed with DLBCL and an IPI score of equal to or greater than three will be eligible for inclusion in this study, provided they consent to receive the standard R-CHOP (Rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) regimen, followed by ASCT. During the interim evaluation, patients achieving complete response (CR) as determined by computed tomography (CT), or complete metabolic response (CMR) as determined by positron emission tomography-computed tomography (PET-CT), will be followed up for up to two years after completing the R-CHOP regimen followed by ASCT. Patients achieving partial response (PR) as determined by CT, or partial metabolic response (PMR) as determined by PET-CT, and who are willing to receive Pola-R-CHP (Polatuzumab vedotin, rituximab, cyclophosphamide, hydroxydaunomycin, and prednisone) as the following treatment regimen followed by ASCT with Pola-BEAM (Polatuzumab vedotin, carmustine/bendamustine, etoposide, cytarabine and melphalan) as conditioning regimen, will also be followed up for up to two years. Patients achieving less than a PR or PMR response will be excluded from the study.

Eligibility criteria: Inclusion Criteria:

* Previously untreated participants with cluster of differentiation 20 (CD20)-positive DLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS) including germinal center B-cell type, activated B-cell type; T-cell/histiocyte-rich large B-cell lymphoma; Epstein-Barr virus-positive DLBCL, NOS; anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma; human herpesvirus-8 (HHV8)-positive DLBCL, NOS; High-grade B-cell lymphoma with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma); High-grade B-cell lymphoma, NOS
* Measurable tumor assessed by Lugano Response Criteria
* International Prognostic Index (IPI) score equal to or greater than 3 points
* Adequate hematologic function
* Adequate liver function
* Adequate kidney function
* Left ventricular ejection fraction (LVEF) \>/= 50 percent (%) on cardiac echocardiogram (ECHO)

Exclusion Criteria:

* Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
* Participants with central nervous system (CNS) lymphoma (primary or secondary involvement)
* History of other malignancy that could affect compliance with the protocol or interpretation of results

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Percentage of Participants With complete response (CR) or complete metabolic response (CMR)
timeFrame: 2 years
measure: Percentage of Participants With partial response (PR) or partial metabolic response (PMR)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Jin Lu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: