Bendamustine and Melphalan in Myeloma (BEB-2)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Melphalan
Bendamustine
Sponsored by

About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Bendamustine, Melphalan, ASCT
Eligibility Criteria
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.
Sites / Locations
- Department for Medical Oncology University Hospital/Inselspital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm A (Mel)
Arm B (BenMel)
Arm Description
Melphalan 100mg/m2/day iv days -2 and -1
Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3
Outcomes
Primary Outcome Measures
Complete Remission rate
Number of Patient achieving complete remissions (CR1) at 60 days after ASCT
Secondary Outcome Measures
Adverse events
Number of Patient experiencing toxicities/adverse events assessed according to the CTCAE 4.0 during the study period
Hematologic engraftment after high-dose chemotherapy
Number of Patient achieving 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.
Overall Survival
Overall survival is defined as the time from ASCT until death of any cause or date of last follow-up
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.
Full Information
NCT ID
NCT03187223
First Posted
June 12, 2017
Last Updated
July 29, 2021
Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
Mundipharma Medical Company
1. Study Identification
Unique Protocol Identification Number
NCT03187223
Brief Title
Bendamustine and Melphalan in Myeloma
Acronym
BEB-2
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
July 20, 2017 (Actual)
Primary Completion Date
March 12, 2020 (Actual)
Study Completion Date
May 28, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
Mundipharma Medical Company
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Bendamustine, Melphalan, ASCT
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized prospective non-blinded clinical phase II trial investigating the drugs bendamustine hydrochloride and melphalan.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
121 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (Mel)
Arm Type
Active Comparator
Arm Description
Melphalan 100mg/m2/day iv days -2 and -1
Arm Title
Arm B (BenMel)
Arm Type
Experimental
Arm Description
Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Ribomustin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Complete Remission rate
Description
Number of Patient achieving complete remissions (CR1) at 60 days after ASCT
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Adverse events
Description
Number of Patient experiencing toxicities/adverse events assessed according to the CTCAE 4.0 during the study period
Time Frame
60 days
Title
Hematologic engraftment after high-dose chemotherapy
Description
Number of Patient achieving 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.
Time Frame
30 days
Title
Overall Survival
Description
Overall survival is defined as the time from ASCT until death of any cause or date of last follow-up
Time Frame
24 months
Title
Quality of Life: EORTC Q30 questionnaire
Description
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.
Time Frame
60 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Pabst, MD
Organizational Affiliation
Department of Medical Oncology, University Hospital Bern
Official's Role
Study Chair
Facility Information:
Facility Name
Department for Medical Oncology University Hospital/Inselspital
City
Berne
ZIP/Postal Code
3010
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Yes
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Bendamustine and Melphalan in Myeloma
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