UARK 2003-25: A Study of Intravenous (IV) Busulfan (Busulfex®) in Multiple Myeloma Patients

Study Overview
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Brief Summary
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The purpose of this study is to find out if patients with high risk disease because of age or kidney status can be treated more safely with a drug called Busulfex® followed by autologous transplant compared to treatment with the standard drug called melphalan, which has been shown to be quite difficult to tolerate in patients with poor kidney function and patients over the age of 65 when given in high doses.

Detailed Description
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This trial will determine the maximal dose of Busulfex® that can be given in a two, three, or four day period with acceptable toxicity to myeloma patients, who either are > or = 65 years of age or have renal insufficiency, defined as creatinine > 3g/dL or creatinine clearance < 30 ml/min.

Official Title
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UARK 2003-25: A Phase I/II Open Label Study of IV Busulfan (Busulfex®) in Multiple Myeloma Patients Older Than 65 Years of Age or With Renal Insufficiency

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Busulfan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have symptomatic multiple myeloma requiring treatment Patients must have been approved for single or tandem autologous transplant Patients must be > or = 65 years of age or diagnosed with renal insufficiency, defined as having a creatinine > 3 mg/dl or a creatinine clearance < 30 ml/minute Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted, Patients must have an ECHO or MUGA performed within 60 days prior to registration, LVEF > 40%. Bilirubin, SGOT, SGPT must be less than 1.5 times the upper limit of normal Patients must have evaluable myeloma marker for response such as: *Serum M protein >1g/dl or urine M protein >1g/24 hours and/or; *Bone marrow plasmacytosis with >20% plasma cells and/or; *Extramedullary plasmacytosis; *MRI/PET scan has focal lesions due to myeloma. Patients must be able to receive full doses of DT-PACE, in the opinion of the treating investigator, with the exception of cisplatin. Patients must have a performance status of 0-2 based on SWOG criteria unless the patient's status is due to active myeloma All patients must be informed of the investigational nature of the study and have signed an IRB-approved informed consent in accordance with institutional and federal guidelines. Exclusion Criteria: Serum transaminases > 1.5 x ULN and direct bilirubin > 1.5 mg/dl HIV positive or active Hepatitis B or Hepatitis C infection; (if serology is positive a quantitative PCR will be done). Patients with a prior malignancy in whom life expectancy is more likely to be determined by the prior malignancy than the myeloma. Patients must not currently be receiving therapy for the prior malignancy. Pregnant or nursing women. Women of childbearing potential must have a negative pregnancy test documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

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<br>study-specific treatment: Busulfex according to study design: Level I 3.2 mg/kg over 6 hours x 2 days Level II 3.2 mg/kg over 6 hours x 3 days Level III 3.2 mg/kg over 6 hours x 4 days Level IV 4.3 mg/kg over 6 hours x 3 days Level V 5.6 mg/kg over 6 hours x 2 days Level VI 6.4 mg/kg over 6 hours x 2 days | Drug: Busulfan<br>* Dexamethasone 40 mg PO 1-4 Thalidomide 200 mg PO 1-6 Cisplatin* 10 mg/m, Continuous infusion 1-4 Adriamycin** 10 mg/m2, Continuous infusion 1-4 Cyclophosphamide 400 mg/2, Continuous infusion 1-4 Etoposide 40 mg/m2, Continuous infusion 1-4 All doses will be based on calculated body weight (actual weight + ideal body weight ÷ 2) and height, and not to exceed a BSA of 2.0 m2 The daily dose of cyclophosphamide, etoposide, and cisplatin will be mixed in a 1L bag of NS to be UAMS infused over 24 hours. Adriamycin will be mixed in at least 50cc D5W to be infused over 24 hours<br>* Other names: Busulfex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Dose of Busulfex® Given in a 2, 3, or 4 Day Period With Acceptable Toxicity to Myeloma Patients | maximal dose of Busulfex® that can be given in a two, three, or four day period with acceptable toxicity to myeloma patients, who either are > or = 65 years of age or have renal insufficiency, defined as creatinine > 3g/dL or creatinine clearance < 30 ml/min | three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloma, MM