Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM)
Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM)
In this protocol, the investigators hypothesize that the combination of intravenous busulfan
 and melphalan with carfilzomib will be an effective preparative regimen with acceptable
 toxicity for participants with multiple myeloma who are candidates for autologous stem cell
 transplantation. To test this hypothesis, the investigators designed a phase I/II trial
 combining IV busulfan 130 mg/m2 plus melphalan 140 mg combined with escalating doses of
 carfilzomib ranging from 20 mg/m2 to 45 mg/m2. These results will be compared with the
 center's historical controls of participants treated with melphalan, busulfan and bortezomib.
Participants enrolled in this study protocol will receive daily intravenous (IV) infusions of
 carfilzomib for a total of 4 days (Day-9, -8 and Days -2, -1). The first two daily infusions
 will be given at a fixed dose of 20 mg/m2 and the final two doses will be escalated from the
 standard dose of 27 mg/m2 to 56 mg/m2 in a Phase I design, based on toxicity. The busulfan
 will be administered for 2 days over 3 hours from D-7, -6, at 130 mg/m2 . This dose was found
 to be safe and equivalent to the standard daily dose of 3.2 mg/kg. The 3rd and 4th daily
 doses of IV Busulfan will be adjusted in order to yield a systemic plasma drug exposure
 represented by a daily area under the plasma concentration versus time curve (AUC) of
 approximately 5,000 millimoles-minute per dose (mM-min). These targeted plasma concentration
 of IV busulfan will be based on pharmacokinetics studies performed during the first day of IV
 busulfan. Melphalan will be given at a dose of 140 mg/m2 on Day -3. Each cohort will start
 with a goal of accruing three patients to determine the dose limiting toxicity.
Inclusion Criteria:

 -  Participants must be greater than or equal to 18 years of age.

 -  Participants must have been diagnosed with multiple myeloma in a first or subsequent
 remission and have undergone a successful pre-transplant work up and are otherwise
 eligible for an autotransplant with a busulfan/melphalan preparative regimen at Loyola
 University Medical Center.

 -  Participants may receive this preparative regimen if in first or subsequent remission.
 Participants may enter if they have received a prior autologous stem cell transplant
 and this therapy produced a remission that lasted greater than 18 months before
 progression of disease. Participants who have undergone prior allogeneic
 transplantation are excluded.

 -  All participants must have responsive disease as defined by a Partial Response or
 greater to most recent conventional regimen.

 -  Participants receiving prior carfilzomib will be eligible for inclusion provided they
 demonstrated responsive disease to this agent and either had a remission that lasted
 greater than 6 months after its discontinuance, or if in remission after a carfilzomib
 containing regimen administered to qualify for transplant.

 -  Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status
 (PS) less than or equal to 2.

 -  Acceptable heart function test.

 Exclusion Criteria:

 -  Participants must not have below normal kidney function.

 -  Participants must not have below normal liver function.

 -  Participants must not have active bacterial, fungal, or viral infection.

 -  Participants must not have severe lung function.

 -  Participants must not have Grade 2 or greater peripheral neuropathy.

 -  Participants must not have uncontrolled hypertension.