Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Giving high-dose chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. An autologous stem cell transplant may be able to replace the blood-forming cells that were destroyed by the chemotherapy. PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide followed by an autologous stem cell transplant works in treating patients with multiple myeloma.

Detailed Description
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OBJECTIVES: Primary To compare relapse-free survival and overall survival of patients with multiple myeloma treated with IV busulfan vs historical control patients treated with oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation. Secondary To compare pulmonary toxicity rates of IV busulfan vs oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation. OUTLINE: Patients receive high-dose busulfan IV every 6 hours on days -8 to -4 and high-dose cyclophosphamide IV over 4 hours on days -3 and -2. Patients undergo autologous hematopoietic stem cell transplantation on day 0. After completion of study treatment, patients are followed up periodically.

Official Title
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A Study of Outcomes and Toxicity of Busulfex as Part of a High Dose Chemotherapy Preparative Regimen in Autologous Hematopoietic Stem Cell Transplantation for Patients With Plasma Cell Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Drug: busulfan
* Drug: cyclophosphamide
* Procedure: autologous hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Patients with a diagnosis of plasma cell myeloma Patients with cardiac ejection fraction >= 45% or clearance by Cleveland Clinic Faculty (CCF) cardiologist Patients with diffusion capacity of carbon monoxide (DLCO) >= 45% predicted or clearance by CCF pulmonologist Patient with previously harvested peripheral blood progenitor cells with a minimum of 2 x 10^6 CD 34+ cells/kg harvested EXCLUSION CRITERIA: Patients receiving total body irradiation Non-myeloablative/reduced-intensity conditioning Pregnant and breast feeding patients Human immunodeficiency virus (HIV) positive Patients with serum creatinine > 2.0 Prior Hematopoietic Stem Cell (HSC) transplant

Ages Eligible for Study
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Minimum Age: 18 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: Busulfan Treatment<br> | Drug: busulfan<br>* IV busulfan 0.8 mg/kg every 6 hours x 16 doses<br>* Other names: Myelosan;Drug: cyclophosphamide<br>* IV cyclophosphamide 60 mg/kg over 4 hours x 2 days<br>* Other names: Enduxan;Procedure: autologous hematopoietic stem cell transplantation<br>* infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free Survival | Number of participants without progressive disease at the end of the study period, using the definitions for complete response, partial response and progressive disease from the International Myeloma Working Group . | at 6 months | 
| Overall Survival | Number of patients alive at the end of the study period | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Toxicity | Toxicity criteria will be assessed and graded according to the National Cancer Institute (NCI) Common Terminology Criteria (CTC) v3.0. Estimated using exact 95% binomial confidence intervals. | At 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma