Bortezomib-bendamustine-melphalan vs Melphalan for Multiple Myeloma

Study Purpose

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.

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.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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 ASCT in first line treatment.

- 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.

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.	NCT06245629
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.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Uppsala University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Honar Cherif, MD, PhD
Principal Investigator Affiliation	Uppsala University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Myeloma Multiple

Additional Details

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 time to next treatment (TNT) after ASCT2 for BBM and HDM-treated patients.

- Mean progression free survival (PFS) after ASCT2 for BBM and HDM-treated patients.

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

Secondary endpoints.

- Depth of best response (stable disease (SD), partial response (PR), very good partial response (VGPR), complete remission (CR), stringent complete remission (sCR)) after ASCT2.

- Overall survival at 2 and 3 years after ASCT2.

- Treatment related mortality at ASCT2.

- Duration of neutropenia (ANC < 0,5) at ASCT2.

- Time until engraftment.

- Duration of hospitalization after stem cell infusion at ASCT2.

- 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.

Arms & Interventions

Arms

: Bortezomib-bendamustine-melphalan

Myeloma patients receiving bortezomib-bendamustine-melphalan at autologous hematopoietic stem cell transplantation first relapse.

: high-dose melphalan

Myeloma patients receiving high-dose melphalan at autologous hematopoietic stem cell transplantation at first relapse.

Interventions

Drug: - Bortezomib-bendamustine-melphalan

The aim of this retrospective cohort study is to evaluate the efficacy and safety of the conditioning regimen BBM compared to HDM in the setting of relapsed multiple myeloma.

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Thomas Silfverberg, MD

thomas.silfverberg@regiondalarna.se

+4623492000

For additional contact information, you can also visit the trial on clinicaltrials.gov.

Clinical Trial Finder