Multiple MyelomaPhase 2BEB-2NCT03187223
Bendamustine and Melphalan in Myeloma
A Phase 2 study testing Melphalan and Bendamustine in people with Multiple Myeloma, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Melphalan and Bendamustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSwitzerland
- Study dates
- 20 Jul 2017to 28 May 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Department for Medical Oncology University Hospital/Inselspital
Bern, 3010
About this study
Official title: 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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Melphalan, Bendamustine
- Keywords
- Multiple Myeloma, Bendamustine, Melphalan, ASCT
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelphalanDrug
Also called Alkeran
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.
BendamustineDrug
Also called Ribomustin
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Mel) | Active comparator | Melphalan 100mg/m2/day iv days -2 and -1 Receives: Drug: Melphalan |
| Arm B (BenMel) | Experimental | Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 Receives: Drug: Melphalan; Drug: Bendamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission Rate
Number of Patient achieving complete remissions (CR1) at 60 days after ASCT
Measured: 60 days
Secondary outcomes (4)
Adverse Events
Number of Patient experiencing toxicities/adverse events assessed according to the CTCAE 4.0 during the study period
Measured: 60 days
Hematologic Engraftment After High-dose Chemotherapy
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.
Measured: 30 days
Overall Survival
Overall survival - Percentage of Participants Alive at 12 Months
Measured: 12 months
Quality of Life: EORTC Q30 Questionnaire
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.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start20 Jul 2017
- Primary completion12 Mar 2020
- Study completion28 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized prospective non-blinded clinical phase II trial investigating the drugs bendamustine hydrochloride and melphalan.
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Mundipharma Medical Company
- Responsible party
- Sponsor
- Investigators
- Thomas Pabst, MD, Study chair, Department of Medical Oncology, University Hospital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03187223
- Sponsor's protocol ID
- BEB-2 Trial
- Acronym
- BEB-2
- Status last verified
- Jan 2025
- First submitted
- 12 Jun 2017
- Last updated
- 30 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial Comparing Bendamustine and Melphalan With Melphalan Alone as Conditioning Regimen for Autologous Stem Cell Transplantation (ASCT) in Myeloma Patients
- ClinicalTrials.gov ID
- NCT03187223
- Acronym / sponsor ID
- BEB-2 / BEB-2 Trial
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Bendamustine, Melphalan, ASCT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Mundipharma Medical Company
- Study start
- 20 Jul 2017 (actual)
- Primary completion
- 12 Mar 2020 (actual)
- Study completion
- 28 May 2020 (actual)
- First posted
- 14 Jun 2017 (actual)
- Results
- Posted 30 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized prospective non-blinded clinical phase II trial investigating the drugs bendamustine hydrochloride and melphalan.
| Arm | Type | Receives |
|---|---|---|
| Arm A (Mel) | Active comparator | Drug: MelphalanMelphalan 100mg/m2/day iv days -2 and -1 |
| Arm B (BenMel) | Experimental | Drug: Melphalan, Drug: BendamustineMelphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelphalanAlso: AlkeranHigh-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. | Drug | Arm A (Mel), Arm B (BenMel) |
| BendamustineAlso: RibomustinHigh-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. | Drug | Arm B (BenMel) |
Primary outcome
Complete Remission Rate
Time frame: 60 days
Number of Patient achieving complete remissions (CR1) at 60 days after ASCT
4 secondary outcomes
Adverse Events
Time frame: 60 days
Hematologic Engraftment After High-dose Chemotherapy
Time frame: 30 days
Overall Survival
Time frame: 12 months
Quality of Life: EORTC Q30 Questionnaire
Time frame: 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Pabst, MD study chair
Department of Medical Oncology, University Hospital Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melphalan and Bendamustine in people with Multiple Myeloma, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission Rate (time frame: 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.