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High Dose Chemotherapy Using BeEAM for Autologous Transplant in Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
BeEAM
Sponsored by
Northside Hospital, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple myeloma, hematopoietic stem cell transplant

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Blood and Marrow Transplant Group of Georgia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BeEAM

Arm Description

Bendaumustine, Etoposide, Cytrabine and Melphalan in autologous transplant for multiple myeloma

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Patients With Overall Survival Post-transplant
Number of Patients With Progression-free Survival
Number of Patients Who Relapsed After Transplant

Full Information

First Posted
March 11, 2015
Last Updated
May 17, 2023
Sponsor
Northside Hospital, Inc.
Collaborators
Teva Pharmaceuticals USA
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1. Study Identification

Unique Protocol Identification Number
NCT02416206
Brief Title
High Dose Chemotherapy Using BeEAM for Autologous Transplant in Multiple Myeloma
Official Title
A Phase II Trial of High-dose Bendamustine, Etoposide, Cytarabine, and Melphalan (BeEAM) in the Up-front Treatment of Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
April 27, 2015 (Actual)
Primary Completion Date
March 26, 2020 (Actual)
Study Completion Date
April 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northside Hospital, Inc.
Collaborators
Teva Pharmaceuticals USA

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple myeloma, hematopoietic stem cell transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BeEAM
Arm Type
Experimental
Arm Description
Bendaumustine, Etoposide, Cytrabine and Melphalan in autologous transplant for multiple myeloma
Intervention Type
Drug
Intervention Name(s)
BeEAM
Intervention Description
BeEAM
Primary Outcome Measure Information:
Title
To Estimate the Response at Day 100 Following Transplant (Rate of CR)
Description
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
Secondary Outcome Measure Information:
Title
Number of Patients With Overall Survival Post-transplant
Time Frame
3 years
Title
Number of Patients With Progression-free Survival
Time Frame
3 years
Title
Number of Patients Who Relapsed After Transplant
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott R Solomon, MD
Organizational Affiliation
Northside Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Blood and Marrow Transplant Group of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States

12. IPD Sharing Statement

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High Dose Chemotherapy Using BeEAM for Autologous Transplant in Multiple Myeloma

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