Trial Outcomes & Findings for Bendamustine and Melphalan in Myeloma (NCT NCT03187223)

NCT ID: NCT03187223

Last Updated: 2025-01-30

Results Overview

Number of Patient achieving complete remissions (CR1) at 60 days after ASCT

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 120 participants
• Primary outcome timeframe: 60 days
• Results posted on: 2025-01-30

Participant Flow

Participant milestones

Measure	Arm A (Mel) Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.
Overall Study STARTED	60	60
Overall Study COMPLETED	60	60
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Arm A (Mel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=60 Participants	0 Participants n=60 Participants	0 Participants n=120 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=60 Participants	29 Participants n=60 Participants	65 Participants n=120 Participants
Age, Categorical >=65 years	24 Participants n=60 Participants	31 Participants n=60 Participants	55 Participants n=120 Participants
Age, Continuous	62 years n=60 Participants	65 years n=60 Participants	63 years n=120 Participants
Sex: Female, Male Female	25 Participants n=60 Participants	19 Participants n=60 Participants	44 Participants n=120 Participants
Sex: Female, Male Male	35 Participants n=60 Participants	41 Participants n=60 Participants	76 Participants n=120 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Switzerland	60 participants n=60 Participants	60 participants n=60 Participants	120 participants n=120 Participants

PRIMARY outcome

Timeframe: 60 days

Population: Response rates were assessed according to the International Myeloma Working Group (IMWG). Bone marrow (BM) was assessed by cytomorphology, histopathology with immunohistochemistry, and immunophenotyping by multiparameter flow cytometry (MFC) for detection of measurable residual disease (MRD). MRD negativity was defined by less than 10-5 aberrant plasma cells after measuring at least 1000000 nucleated cells.

Number of Patient achieving complete remissions (CR1) at 60 days after ASCT

Outcome measures

Measure	Arm A (Mel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.
Complete Remission Rate	31 Participants	42 Participants

SECONDARY outcome

Timeframe: 60 days

Population: Clinical assessment and documentation of toxicities exceeding grade II during hospitalization were performed until 60 days after ASCT.

Number of Patient experiencing toxicities/adverse events assessed according to the CTCAE 4.0 during the study period

Outcome measures

Measure	Arm A (Mel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.
Adverse Events	36 Participants	43 Participants

SECONDARY outcome

Timeframe: 30 days

Population: Time to neutrophil engraftment was defined as the duration between day 0 and the first 3 days of neutrophils \>0.5 × 109/L after ASCT.

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.

Outcome measures

Measure	Arm A (Mel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.
Hematologic Engraftment After High-dose Chemotherapy	12 days Interval 10.0 to 18.0	11 days Interval 10.0 to 60.0

SECONDARY outcome

Timeframe: 12 months

Overall survival - Percentage of Participants Alive at 12 Months

Outcome measures

Measure	Arm A (Mel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) n=60 Participants Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.
Overall Survival	96 percentage of participants	96 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Mel)

Serious events: 9 serious events

Other events: 36 other events

Deaths: 0 deaths

Arm B (BenMel)

Serious events: 12 serious events

Other events: 43 other events

Deaths: 1 deaths

Serious adverse events

Measure	Arm A (Mel) n=60 participants at risk Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) n=60 participants at risk Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.
Cardiac disorders atrial fibrillation	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Infections and infestations fever unkown origin	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Nervous system disorders neuropathy	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
General disorders weakness	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Respiratory, thoracic and mediastinal disorders respiratory failue	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
General disorders fever	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Renal and urinary disorders renal failure	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Gastrointestinal disorders colitis	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Infections and infestations respiratory infection	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Infections and infestations Infection	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Cardiac disorders right ventricular disfunction	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Respiratory, thoracic and mediastinal disorders Respiratory insufficiency	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Gastrointestinal disorders Esophagitis	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Nervous system disorders Confusion	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Gastrointestinal disorders Pancolitis	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
General disorders weight loss	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Skin and subcutaneous tissue disorders Panaritium	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Infections and infestations Septic Schock	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Vascular disorders Thromboembolic event	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Respiratory, thoracic and mediastinal disorders ARDS	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	1.7% 1/60 • Number of events 1 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days

Other adverse events

Measure	Arm A (Mel) n=60 participants at risk Melphalan 100mg/m2/day iv days -2 and -1 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.	Arm B (BenMel) n=60 participants at risk Melphalan 100mg/m2/day iv days -2 and -1 Bendamustine 200mg/m2/day iv days -4 and -3 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. 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.
Gastrointestinal disorders Gastrointestinal disordes	51.7% 31/60 • Number of events 31 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	50.0% 30/60 • Number of events 30 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Metabolism and nutrition disorders Metabolic and nutritional disorders	16.7% 10/60 • Number of events 10 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	33.3% 20/60 • Number of events 20 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
Cardiac disorders Cardiac and thromboembolic disorders	8.3% 5/60 • Number of events 5 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	5.0% 3/60 • Number of events 3 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
General disorders Weight loss >10%	0.00% 0/60 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	8.3% 5/60 • Number of events 5 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days
General disorders Engraftment syndrome	5.0% 3/60 • Number of events 3 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days	3.3% 2/60 • Number of events 2 • Deaths were assessed up to 24 months. Adverse Events were assessed through 60 days

Additional Information

Prof Dr. Thomas Pabst

Department of Medical Oncology, Inselspital, University Hospital and University of Bern, Bern, Switzerland

Phone: +41 31 63 2 84 30

Email: Thomas.Pabst@insel.ch

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place