Clinical trial NCT06245629: Bortezomib-bendamustine-melphalan vs Melphalan for Multiple Myeloma
Official title: Bortezomib-bendamustine-melphalan vs High-dose Melphalan in Autologous Hematopoietic Stem Cell Transplantation for Relapsed Multiple Myeloma - a Single Center Retrospective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myeloma Multiple
Keywords: Autologous hematopoietic stem cell transplantation
Melphalan
Bendamustine
Bortezomib
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Uppsala County Council, Sweden
name: Dalarna County Council, Sweden
First posted: 2024-02-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Fifty consecutive patients, who were referred to UUH for a second ASCT after relapse in multiple myeloma following HDM and ASCT between 1 Nov 2011 and 30 Jun 2018 and who received conditioning with bortezomib-bendamustine-melphalan will be included in this study. As a control group, 25 consecutive patients who were treated with HDM prior to 1 Nov 2011 and 25 consecutive patients following 30 Jun 2018. The patients will be identified through the local European Society for Blood and Marrow Transplantation (EBMT) registry at UUH.

Brief summary: This project will evaluate the efficacy and safety of the conditioning regimen bortezomib-bendamustine-melphalan (BBM) in combination with autologous hematopoietic stem cell transplantation (ASCT) in relapsed multiple myeloma given from 2011 to 2018 at Uppsala University Hospital. This approach will be retrospectively compared to high dose melphalan (HDM) in the same setting in the years prior to, and following the BBM-period. Data on efficacy and safety data will be collected through systematic analysis of electronic medical records and from the Swedish Cancer Registry.

Detailed description: Study design This is a retrospective single center cohort study comparing the new conditioning regimen bortezomib-bendamustine-melphalan to standard high-dose melphalan. The data sources will be electronic medical records and prospectively collected data from the Swedish Cancer Registry. The comparison will be analyzed in two parts. First, each patient will be its own control, comparing time to next treatment (TNT) for the first ASCT (always HDM, referred to as ASCT1) and second ASCT (BBM or HDM, referred to as ASCT2), and compare the mean difference between the two cohorts. Secondly, the difference in efficacy and severe adverse events between BBM and HDM at ASCT2 will be compared.

Study population Fifty consecutive patients, who were referred to Uppsala University Hospital (UUH) for a second ASCT after relapse in multiple myeloma following HDM and ASCT between 1 Nov 2011 and 30 Oct 2018 and who received conditioning with bortezomib-bendamustine-melphalan will be included in this study. As a control group, 25 consecutive patients who were treated with HDM prior to 1 Nov 2011 and 25 consecutive patients following 30 Oct 2018. The patients will be identified through the local European Society for Blood and Marrow Transplantation (EBMT) registry at UUH.

UUH is the referral hospital for seven Swedish regions with a total population of 2 151 353 at Dec 31 2022, which constitutes roughly one fifth of the population of Sweden.

Data collection Study data will be collected through systematic analysis of medical records from UUH and all the hospitals referring patients to UUH and from the Swedish Cancer Registry. All severe adverse events (AEs) will be collected until day 100 after ASCT2 according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Primary endpoints

• Mean TNT after ASCT1 and ASCT2 for each individual patient (each patient as its own control), for BBM and HDM-treated patients

Secondary endpoints

* Median time to next treatment (TNT) after ASCT2
* Median progression free survival (PFS) after ASCT2
* Depth of best response (stable disease (SD), partial response (PR), very good partial response (VGPR), complete remission (CR), stringent complete remission (sCR)) after ASCT2
* Median Overall survival after ASCT2
* Treatment related mortality rate at ASCT2
* Mean duration of neutropenia (ANC \< 0,5) at ASCT2
* Mean time until engraftment
* Mean duration of hospitalization after stem cell infusion at ASCT2
* The frequency of all serious adverse events according to version 5.0 of National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) during hospitalization and until day +100 after ASCT2.

Prespecified subgroups will include depth of best response prior to ASCT2, any specific maintenance therapies following ASCT2, patients receiving Granulocyte Colony Stimulating Factor (G-CSF) following ASCT, and patients receiving daratumumab as a part of induction or maintenance therapy at ASCT2.

In addition, an exploratory subgroup analysis is planned for patients with high-risk cytogenetics including p53-aberrations and patients with early relapse after ASCT1 (less than 3 years), although missing data is expected to be high.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of first relapse after previous ASCT for multiple myeloma according to the International Myeloma Working Group.
* Treated with a second ASCT (ASCT2) as part of second line treatment at UUH.
* Conditioning at ASCT2 with bortezomib-bendamustine-melphalan or high-dose melphalan only.

Exclusion Criteria:

* Double (tandem) ASCT in first or second line treatment
* Allogenic haematopoietic stem cell transplantation as part of first or second line therapy
* Failure to meet the minimal dataset, defined as: (date of ASCT1 and ASCT2, date of start of induction treatment for relapsed myeloma prior to ASCT2, medical records from hospitalization for ASCT2, at least one follow-up visit (unless early death before first follow-up visit), date of progression and first treatment of relapsed multiple myeloma after ASCT2.

Primary outcomes:
measure: Mean difference in time to next treatment (TNT) after ASCT1 and ASCT2 for each individual patient
timeFrame: 0.2-18 years
Secondary outcomes:
measure: Median time to next treatment after ASCT2
timeFrame: 0-18 years
measure: Median progression free survival (PFS) after ASCT2
timeFrame: 0-18 years
measure: Median overall survival after ASCT2
timeFrame: 0-18 years
measure: Depth of best response after ASCT2
timeFrame: 0-24 months
measure: Treatment related mortality
timeFrame: 0-12 months
measure: Mean duration of neutropenia at ASCT2
timeFrame: 7-50 days
measure: Mean time until engraftment at ASCT2
timeFrame: 5-50 days
measure: Mean duration of hospitalization at ASCT2
timeFrame: 7-50 days
measure: Frequency of severe adverse events at ASCT2
timeFrame: 100 days
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
Study officials:
affiliation: Uppsala University
name: Honar Cherif, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: