Multiple Myeloma
Conditions
Keywords
multiple myeloma, transplant
Brief summary
In this study the investigators are comparing this standard regimen to the newly established regimen of melphalan and bortezomib.
Detailed description
In this study the investigators are comparing this standard regimen to the newly established regimen of melphalan and bortezomib. Conditioning Regimens: Treatment arm A Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour. Melphalan will be given as a single dose (not split over 2 or more days) and given on day-1. Dosing will be based on body surface area calculated using actual body weight Stem cell infusion: Stem cell infusion will occur on day 0 and will be at least 20 hours after the infusion of melphalan. The infusion of peripheral blood stem cells will be done in accordance with the Blood and Marrow Transplant program standard operating procedures. Filgrastim will be administered at a dose of 5 mcg/kg (rounded to vial size) every other day starting on day+3 then daily starting on day 9 until engraftment (at least). Treatment arm B Bortezomib: Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line. Bortezomib will be administered any time on day -4 and at least 20 hrs after the start of the melphalan infusion on day -1. Dosing will be based on actual body weight. Dexamethasone is administered at a dose of 20 mg IV prior to each bortezomib infusion. Melphalan: Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour. Melphalan will be given as a single dose (not split over 2 or more days) and given of day-2. Dosing will be based body surface area calculated using actual body weight Stem cell infusion: Stem cell infusion will occur on day 0 and will be at least 18 hours after the infusion of the bortezomib. The infusion of peripheral blood stem cells will be done in accordance with the Blood and Marrow Transplant program standard operating procedures. Filgrastim will be administered at a dose of 5 mcg/kg (rounded to vial size) every other day starting on day+3 then daily starting on day 9 until engraftment (at least). Post-transplant Supportive Care will be administered in accordance to the Blood and Marrow Transplant program standard operating procedures.
Interventions
DRUGMelphalan
Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour. Melphalan will be given as a single dose (not split over 2 or more days) and given on day-1. Dosing will be based on body surface area calculated using actual body weight Stem cell infusion: Stem cell infusion will occur on day 0 and will be at least 20 hours after the infusion of melphalan. The infusion of peripheral blood stem cells will be done in accordance with the Blood and Marrow Transplant program standard operating procedures. Filgrastim will be administered at a dose of 5 mcg/kg (rounded to vial size) every other day starting on day+3 then daily starting on day 9 until engraftment (at least).
DRUGBortezomib
Bortezomib: Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line. Bortezomib will be administered any time on day -4 and at least 20 hrs after the start of the melphalan infusion on day -1.
Sponsors
Hackensack Meridian Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of multiple myeloma less than 12 months since initiation of systemic therapy * Age ≥60 years at time of transplantation * KPS 70-100% * Recovery from complications of prior therapy
Exclusion criteria
* Diagnosis other than multiple myeloma * Chemotherapy or radiotherapy within 8 days of initiating treatment in this study * Prior dose-intense therapy within 56 days of initiating treatment in this study * Uncontrolled bacterial, viral, fungal or parasitic infections * Uncontrolled CNS metastases * Known amyloid deposition in heart * Organ dysfunction * LVEF \<40% or cardiac failure not responsive to therapy * FVC, FEV1 or DLCO \< 40% of predicted and/or receiving supplementary continuous oxygen * Evidence of hepatic synthetic dysfunction or total bilirubin \> 2x or AST \> 3x ULN * Measured creatinine \< 20ml/min * Sensory peripheral neuropathy grade 4 within 14 days of enrollment * Karnofsky score \< 70% * Life expectancy limited by other co-morbid illnesses
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate | Participants will be followed post transplant for a minimum of 3 years, and after that may be monitored as part of the study indefinitely | Progression free survival of elderly patients with multiple myeloma treated with either high-dose melphalan versus high-dose melphalan and bortezomib at 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival Rate | 1 year |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichele Donato, MD
John Theurer Cancer Center at Hackensack University Medical Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Auto Transplant High Dose Melphalan Melphalan is administered at a dose of 200mg/m2 by rapid intravenous infusion via a central or peripheral vein over 30 minutes to one hour.
Melphalan will be given as a single dose (not split over 2 or more days) and given on day-1.
Dosing will be based on body surface area calculated using actual body weight | 28 |
| Auto Transplant High Dose Melphalan+Bortezomib Bortezomib:
Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line. Bortezomib will be administered any time on day -4 and at least 20 hrs after the start of the melphalan infusion on day -1.
Bortezomib: Bortezomib:
Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line. Bortezomib will be administered any time on day -4 and at least 20 hrs after the start of the melphalan infusion on day -1. | 31 |
| Total | 59 |
Baseline characteristics
| Characteristic | Auto Transplant High Dose Melphalan | Auto Transplant High Dose Melphalan+Bortezomib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 31 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Continuous | 69 years | 69 years | 69 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 30 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) White | 22 Participants | 28 Participants | 50 Participants |
| Region of Enrollment United States | 28 participants | 31 participants | 59 participants |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Male | 16 Participants | 17 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 28 | 4 / 31 |
| other Total, other adverse events | 0 / 28 | 0 / 31 |
| serious Total, serious adverse events | 13 / 28 | 18 / 31 |
Outcome results
Primary
Progression Free Survival Rate
Progression free survival of elderly patients with multiple myeloma treated with either high-dose melphalan versus high-dose melphalan and bortezomib at 3 years
Time frame: Participants will be followed post transplant for a minimum of 3 years, and after that may be monitored as part of the study indefinitely
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auto Transplant High Dose Melphalan | Progression Free Survival Rate | 13 Participants |
| Auto Transplant High Dose Melphalan+Bortezomib | Progression Free Survival Rate | 11 Participants |
Secondary
Overall Survival Rate
Time frame: 1 year
Population: Overall Survival Rate
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auto Transplant High Dose Melphalan | Overall Survival Rate | 27 Participants |
| Auto Transplant High Dose Melphalan+Bortezomib | Overall Survival Rate | 27 Participants |