Bendamustine and Melphalan in Myeloma (BEB-2)

January 7, 2025 updated by: Insel Gruppe AG, University Hospital Bern

A Randomized Phase II Trial Comparing Bendamustine and Melphalan With Melphalan Alone as Conditioning Regimen for Autologous Stem Cell Transplantation (ASCT) in Myeloma Patients

Two high-dose chemotherapy regimens (melphalan alone versus the combination of melphalan and bendamustine) used for conditioning treatment before autologous stem cell transplantation will be compared in a 1:1 randomization in myeloma patients. The experimental arm is the bendamustine and melphalan (BenMel) combined regimen. The melphalan alone (Mel) regimen is the control (standard) treatment. Despite remarkable progress using novel agents both for induction before ASCT as well for maintenance after ASCT, definite cure in myeloma patients remains exceptional due to residual disease escaping intensive treatment. The aim of the study is to show an improvement of the rate of complete Remission 60 days after ASCT in myeloma patients from 50% with melphalan alone to 65% with the combination of bendamustine and melphalan.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background and Rationale:

High-dose chemotherapy with melphalan and autologous stem cell transplantation (ASCT) remains an integral component of the myeloma treatment algorithm for patients considered eligible for the procedure, nowadays performed in myeloma patients up to the age of 75 years. Despite remarkable progress using novel agents both for induction before ASCT as well for maintenance after ASCT, definite cure in myeloma patients remains exceptional due to residual disease escaping intensive treatment. Martino et al. recently reported data on the feasibility and efficacy of the combination of bendamustine and melphalan (BenMel) as a conditioning regimen to second ASCT in patients with myeloma. In addition, extensive experience is available on the use of bendamustine (200mg/m2/day given on days -7 and -6) together with melphalan (140mg/m2/day day -1) and two additional drugs, cytarabine and etoposide (each on days -5 to -2) in the BeEAM conditioning regimen which is increasingly used as the standard conditioning regimen in lymphoma patients, also in the investigators' clinic, with an acceptable tolerability and safety profile. In summary, these data suggest that combinations of melphalan and bendamustine are usually well tolerated and that the maximum tolerated dose of bendamustine is not reached with the doses of 200mg/m2/day given on two days added to melphalan,etoposide and cytarabine (BeEAM regimen). The investigators therefore suggest in this study to directly compare bendamustine 200 mg/m2/day (on days -4 and -3) plus melphalan 100mg/m2/day (on days -2 and -1) with melphalan 100mg/m2/day (days -2 and -1) in a randomized trial.

Objectives:

Primary objective To show a clinically meaningful improvement by 15% of the rate of complete remission (CR1) 60 days after ASCT in myeloma patients from 50% with melphalan alone to 65% with the combination of bendamustine and melphalan.

Secondary objectives To assess acute and late toxicities/adverse events (CTCAE 4.0) during the study period in patients treated with the combination of bendamustine and melphalan as compared to melphalan alone.

To assess the hematologic engraftment in patients treated with the combination of bendamustine and melphalan as compared to melphalan alone.

To particularly assess early renal toxicity in patients treated with the combination of bendamustine and melphalan as compared to melphalan alone.

To assess differences in overall survival and progression free survival in patients treated with the combination of bendamustine and melphalan as compared to melphalan alone after one year.

To assess the quality of life prior to ASCT and at day 60 assessment thereafter

Outcome:

To assess the rate of complete remission (CR1) 60 days after ASCT in myeloma patients treated with the combination of bendamustine and melphalan as compared to melphalan alone by routine laboratory myeloma parameters (serum M-gradient and light chain ratio) and bone marrow assessments in patients with CR1.

Number of Participants with Rationale: Applying a statistical power of 80% and a one-sided significance level of 20%, 60 evaluable patients will be needed in each group to show a clinically meaningful improvement by 15% of the rate of complete remission (CR1) 60 days after ASCT in myeloma patients, from 50% with melphalan alone to 65% with the combination of bendamustine and melphalan.

Study Duration: The total study duration is 36 months. Study design: Randomized two-arm open-label prospective phase II trial. Monitoring will be performed by the Clinical Trial Unit (CTU) of the University of Berne, Switzerland.

This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP as well as all national legal and regulatory requirements.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Berne, Switzerland, 3010
        • Department for Medical Oncology University Hospital/Inselspital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Myeloma patients after standard first-line induction treatment. A second induction regimen in refractory myeloma patients is allowed.
  • Patients must be considered being fit for subsequent consolidation with high-dose chemotherapy with melphalan with autologous stem cell support.
  • Patients must be aged 18-75 years.
  • Patients must have an ECOG < 3.
  • Patients must have a creatinine clearance ≥ 40 ml/min.
  • Patients must have a LVEF ≥ 40% within three months prior to start of study medication (Echo can be postponed to study treatment visit if clinically indicated).
  • Female patients of child-bearing potential: No known pregnancy (a pregnancy test in female patients of child-bearing potential is not mandatory since patients are already under induction chemotherapy or mobilization chemotherapy, and pregnancy was excluded before starting chemotherapy…)
  • Patients must have given voluntary written informed consent.

Exclusion Criteria:

  • Patients with uncontrolled acute infection.
  • Patients with a transplantation comorbidity index (HCTCI) > 6 points.
  • Patients with concurrent malignant disease with the exception of basalioma/spinalioma of the skin or early-stage cervix carcinoma, or early-stage prostate cancer. Previous treatment for other malignancies (not listed above) must have been terminated at least 24 months before registration and no evidence of active disease shall be documented since then.
  • Patients with major coagulopathy or bleeding disorder.
  • Patients with other serious medical condition that could potentially interfere with the completion of treatment according to this protocol or that would impair tolerance to therapy or prolong hematological recovery.
  • Lack of patient cooperation to allow study treatment as outlined in this protocol.
  • Pregnancy or lactating female patients.
  • The use of any anti-cancer investigational agents within 14 days prior to the expected start of trial treatment.
  • Contraindications and hypersensitivity to any of the active chemotherapy compounds.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Arm A (Mel)
Melphalan 100mg/m2/day iv days -2 and -1
Drug: Melphalan
High-dose chemotherapy regimen for conditioning treatment before autologous stem cell Transplantation. Patients will receive melphalan at a total dose of 200mg/m2, divided in two doses of 100mg/m2/day on days -2 and -1, with the ASCT at day 0.
Other Names:
  • Alkeran
Experimental: Arm B (BenMel)
Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3
Drug: Melphalan
High-dose chemotherapy regimen for conditioning treatment before autologous stem cell Transplantation. Patients will receive melphalan at a total dose of 200mg/m2, divided in two doses of 100mg/m2/day on days -2 and -1, with the ASCT at day 0.
Other Names:
  • Alkeran
Drug: Bendamustine
High-dose chemotherapy regimen for conditioning treatment before autologous stem cell Transplantation. Patients will receive bendamustine at a total dose of 400mg/m2, divided in two doses of 200mg/m2/day on days -4 and -3. Melphalan is given at a total dose of 200mg/m2, divided in two doses of 100mg/m2/day, each on days -2 and -1, with the ASCT at day 0.
Other Names:
  • Ribomustin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Complete Remission Rate
Time Frame: 60 days
Number of Patient achieving complete remissions (CR1) at 60 days after ASCT
60 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 60 days
Number of Patient experiencing toxicities/adverse events assessed according to the CTCAE 4.0 during the study period
60 days
Hematologic Engraftment After High-dose Chemotherapy
Time Frame: 30 days
Number of days needed to achieve hematologic engraftment after high-dose chemotherapy induced myelosuppression is defined as the first day of neutrophils rising again above 0.5 G/l, and of platelets rising again above 20 G/L in the absence of platelet transfusions in the previous 3 days.
30 days
Overall Survival
Time Frame: 12 months
Overall survival - Percentage of Participants Alive at 12 Months
12 months
Quality of Life: EORTC Q30 Questionnaire
Time Frame: 60 days
Assessment of quality of life prior to ASCT and 60 days thereafter. The EORTC Q30 questionnaire will be given to patients at screening and at the day 60 assessment.
60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Insel Gruppe AG, University Hospital Bern

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Mundipharma Medical Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Thomas Pabst, MD, Department of Medical Oncology, University Hospital Bern

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 20, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 12, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 28, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 14, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BEB-2 Trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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