High-Dose Gemcitabine, Busulfan and Melphalan With Hematopoietic-Cell Support for Patients With Poor-Risk Myeloma
Condition: Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Palifermin; Dexamethasone; Gemcitabine; Busulfan; Melphalan; Stem Cell Transplant; G-CSF
Intervention description: 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.; 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient.; 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.; 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan AUC 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.; 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.; On Day 0, stem cells returned to body by vein over 30-60 minutes.; 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Intervention MeSH terms: Dexamethasone; Gemcitabine; Melphalan; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Autologous Hematopoietic-Cell Support; Stem Cell Transplant; Busulfan; Myleran; Busulfex; Gemcitabine; Gemzar; Melphalan; Alkeran; Decadron; Dexamethasone; G-CSF; Filgrastim; Neupogen

Summary:

      The goal of this clinical research study is to learn if the combination of gemcitabine,
      busulfan, and melphalan, when given before a stem cell transplant, can help to control
      refractory myeloma. The safety of this study treatment will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18 to 70 years.

          2. Patients with myeloma treated with first-line therapy including lenalidomide,
             bortezomib or thalidomide, and one or more of the following: 2.1) M paraprotein
             greater than 1 g/dL at HDC. 2.2) Less than partial response to first-line therapy.
             2.3) Relapse after first-line therapy. 2.4) Relapse after a prior autologous stem-cell
             transplant.

          3. Adequate renal function, as defined by serum creatinine </=1.8 mg/dL and/or estimated
             serum creatinine clearance >/=50 ml/min

          4. Adequate hepatic function, as defined by serum glutamate oxaloacetate transaminase
             (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) </=3 x upper limit of
             normal; serum bilirubin and alkaline phosphatase </=2 x upper limit of normal, unless
             proven to be due to disease involvement.

          5. Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced
             vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) >/=50%
             of expected corrected for hemoglobin and/or volume.

          6. Adequate cardiac function with left ventricular ejection fraction >/=40%. No
             uncontrolled arrhythmias or symptomatic cardiac disease.

          7. Zubrod performance status <2.

          8. Negative Beta human chorionic gonadotropin (HCG) text in a woman with child-bearing
             potential, defined as not post-menopausal for 12 months or no previous surgical
             sterilization

        Exclusion Criteria:

          1. Patients with grade >/= 3 non-hematologic toxicity from previous therapy that has not
             resolved to </= grade 1.

          2. Patients with prior whole brain irradiation

          3. Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA
             >/=10,000 copies/mL, or >/= 2,000 IU/mL).

          4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic
             hepatitis C or positive hepatitis C serology.

          5. Active infection requiring parenteral antibiotics.

          6. HIV infection, unless the patient is receiving effective antiretroviral therapy with
             undetectable viral load and normal cluster of differentiation 4 (CD4) counts

          7. Patients having received radiation therapy to head and neck (excluding eyes), and
             internal organs of chest, abdomen or pelvis in the month prior to enrollment.