Bortezomib-bendamustine-melphalan vs Melphalan for Multiple Myeloma

Myeloma Multiple Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06245629
• Other study ID #: 2023-04134-01
• Status: Not yet recruiting
• Start date: February 1, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: January 2024
• Source: Uppsala University
• Contact: Thomas Silfverberg, MD
• Phone: +4623492000
• Email: thomas.silfverberg[@]regiondalarna.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: September 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Myeloma Multiple
• Neoplasms, Plasma Cell

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Uppsala University	Dalarna County Council, Sweden, Uppsala County Council, Sweden

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean time to next treatment (TNT)	Average time to next myeloma treatment after autologous stem cell transplantation	0.2-10 years
Primary	Mean progression free survival (PFS)	Average time to progression	0.2-10 years
Secondary	Depth of best response	Best result after given treatment for myeloma	0-3 months
Secondary	Overall survival	Survival until death from any cause	at 2 and 3 years
Secondary	Treatment related mortality	Death due to any transplantation-related cause other than disease progression.	0-12 months
Secondary	Duration of neutropenia	Absolute neutrophil count (ANC) <0.5 x10^9	7-50 days
Secondary	Time until engraftment	Days from ASCT until ANC of 0.5 x 109/L or higher and total platelet count of 20 x 109/L and rising, without transfusion of thrombocytes.	5-50 days
Secondary	Duration of hospitalization	Days from ASCT until discharge	7-50 days
Secondary	Frequency of severe adverse events	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.	100 days