Multiple Myeloma
Conditions
Keywords
Multiple myeloma, hematopoietic stem cell transplant
Brief summary
High-dose chemotherapy and autologous stem cell transplantation (ASCT) as part of the up-front treatment of patients with multiple myeloma has been associated with improved disease-free and overall survival in multiple large randomized controlled trials. Following 3-6 cycles of standard induction therapy with biologic agents, consolidation with high dose Melphalan and ASCT has become the standard-of-care approach for fit myeloma patients up to 70 years of age. Single-agent high-dose Melphalan (200mg/m2) is currently the standard-of-care preparative regimen prior to autologous transplant in Myeloma. Historical studies utilizing Busulfan- or Total Body Irradiation-based preparative regimens have yielded similar results to single-agent Melphalan with higher toxicity.
Detailed description
Myeloma patients, following up-front induction therapy, will receive an ASCT following a high-dose bendamustine-based preparative regimen (BeEAM). The primary endpoint of this trial will be the rate of CR at day 100 post-transplant. Experience from the literature, as well as results from our institution, suggests that following ASCT for the upfront treatment of myeloma, the rate of CR at day 100 post-transplant is approximately 45%. It is hoped that under this protocol, this rate will be at least 65%. Thus we statistically formalize this study by testing the null hypothesis that p, the CR rate is 0.65 or more versus the alternative hypothesis that p is less than 0.45. A sample size of 65 pts gives 90% power with an alpha=0.05, using the formula for a one sample binomial (two-sided) test of a proportion.
Interventions
DRUGBeEAM
BeEAM
Sponsors
Teva Pharmaceuticals USA
Northside Hospital, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 - 70 years * Karnofsky status ≥ 70% * Diagnosis of Multiple Myeloma * Within 9 months of the start of induction chemotherapy and no evidence of relapse or progression. * Availability of Cryopreserved peripheral blood stem cells with a CD34 dose of at least 2x106/kg.
Exclusion criteria
* Poor cardiac function: left ventricular ejection fraction \<40% * Poor pulmonary function: FEV1, FVC, or DLCO \<40% predicted * Poor liver function: bilirubin \>2.5 mg/dl (not due to hemolysis, Gilbert's or primary malignancy), AST/ALT \> 3X ULN * Poor renal function: Creatinine \>2.0 mg/dl or creatinine clearance \< 40 mL/min (calculated creatinine clearance is permitted) * Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. * Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception * Patients who have any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Estimate the Response at Day 100 Following Transplant (Rate of CR) | Day 100 | Using IMWG criteria: PR (partial response) noted as \>50% reduction of serum M-protein and reduction in 24hr urinary M-protein by \>90% or to \<200mg/24h; VgPR (very good partial response) noted as serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M-protein plus urine M-protein level \<100mg/24h; CR (complete response) noted as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow; sCR (stringent complete response) noted as CR defined above plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Patients With Overall Survival Post-transplant | 3 years |
| Number of Patients With Progression-free Survival | 3 years |
| Number of Patients Who Relapsed After Transplant | 3 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BeEAM Bendaumustine, Etoposide, Cytrabine and Melphalan in autologous transplant for multiple myeloma
BeEAM: BeEAM | 65 |
| Total | 65 |
Baseline characteristics
| Characteristic | BeEAM |
|---|---|
| Age, Continuous | 59 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 65 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 65 |
| other Total, other adverse events | 17 / 65 |
| serious Total, serious adverse events | 48 / 65 |
Outcome results
Primary
To Estimate the Response at Day 100 Following Transplant (Rate of CR)
Using IMWG criteria: PR (partial response) noted as \>50% reduction of serum M-protein and reduction in 24hr urinary M-protein by \>90% or to \<200mg/24h; VgPR (very good partial response) noted as serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M-protein plus urine M-protein level \<100mg/24h; CR (complete response) noted as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow; sCR (stringent complete response) noted as CR defined above plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Time frame: Day 100
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BeEAM | To Estimate the Response at Day 100 Following Transplant (Rate of CR) | Complete Response (CR1) | 26 Participants |
| BeEAM | To Estimate the Response at Day 100 Following Transplant (Rate of CR) | Very Good Partial Response (VGPR1) | 32 Participants |
| BeEAM | To Estimate the Response at Day 100 Following Transplant (Rate of CR) | Partial Response (PR1) | 7 Participants |
Secondary
Number of Patients Who Relapsed After Transplant
Time frame: 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BeEAM | Number of Patients Who Relapsed After Transplant | 28 Participants |
Secondary
Number of Patients With Overall Survival Post-transplant
Time frame: 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BeEAM | Number of Patients With Overall Survival Post-transplant | 60 Participants |
Secondary
Number of Patients With Progression-free Survival
Time frame: 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BeEAM | Number of Patients With Progression-free Survival | 37 Participants |