High Dose Chemotherapy Using BeEAM for Autologous Transplant in Multiple Myeloma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial of High-dose Bendamustine, Etoposide, Cytarabine, and Melphalan (BeEAM) in the Up-front Treatment of Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: BeEAM


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BeEAM<br>Bendaumustine, Etoposide, Cytrabine and Melphalan in autologous transplant for multiple myeloma | Drug: BeEAM<br>* BeEAM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple myeloma, hematopoietic stem cell transplant