High Dose Chemotherapy Using BeEAM for Autologous Transplant in Multiple Myeloma

Phase 2

Completed

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
BeEAM	BeEAM	Bendaumustine, Etoposide, Cytrabine and Melphalan in autologous transplant for multiple myeloma

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of Patients With Progression-free Survival	3 years
Number of Patients Who Relapsed After Transplant	3 years
Number of Patients With Overall Survival Post-transplant	3 years