A Phase I/II Open Label Study of IV Busulfan (Busulfex®) in Multiple Myeloma Patients 65 Years of Age or Older, or With Renal Insufficiency Undergoing Autologous Transplantation
This study is for first line treatment for multiple myeloma patients in patients >65 years
or have renal insufficiency Busulfan introduces cytopenia much slower than melphalan while
the time to recover after transplantation is the same. The duration of cytopenia with
busulfan should therefore be shorter. Busulfan given in myeloma patients with renal failure
has proven to be effective.
The initial proposed dose level in our study will be 3.2mg/kg of body weight over 6 hours
for 3 days. The next levels will be 3.2mg/kg of body weight over 6 hours for 4 days, 4.3
mg/kg of body weight over 6 hours for 3 days, 5.6 mg/kg of body weight over 6 hours for 2
days, and 6.4 mg/kg of body weight over 6 hours for 2 days. Three patients per group will
be entered at the first level. Further enrollment will be dependent upon toxicities
observed. All dose escalations will be initiated after the PI has reviewed the toxicity data
available on the prior dose levels and confirms that it is safe to proceed to subsequent
dose level(s). Maximum tolerated dose will defined as the dose level immediately below the
dose level at which ≥ 2 of 6 patients experiences a grade 4 non-hematological toxicity that
is unexpected, related, and serious, and it will be evaluated separately for patients > 65
years of age or in patients with renal insufficiency.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
determine MTD of Busulfex given safely over least number of days patients who are either ≥65 years Group 1) or have renal insufficiency (Group 2), defined as creatinine >3mg/dL or creatinine clearance <30 mL/min.
Guido Tricot, MD, PhD
University of Utah
United States: Institutional Review Board