Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma
Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma
This phase I/II trial studies the safety and best dose of melphalan and bortezomib when given
 prior to an autologous stem cell transplant and to see how well they work in treating
 patients with multiple myeloma. Drugs used in chemotherapy, such as melphalan, work in
 different ways to stop the growth of cancer cells, either by killing the cells, by stopping
 them from dividing, or by stopping them from spreading. Bortezomib may help melphalan work
 better by making cancer cells more sensitive to the drug. Giving chemotherapy before an
 autologous hematopoietic stem cell transplant helps kill any cancer cells that are in the
 body and helps make room in the patient's bone marrow for new blood-forming cells (stem
 cells) to grow. After treatment, stem cells are collected from the patient's blood and
 stored. More chemotherapy is then given to prepare the bone marrow for the stem cell
 transplant. The stem cells are then returned to the patient to replace the blood-forming
 cells that were destroyed by the chemotherapy. Giving melphalan together with bortezomib
 prior to autologous hematopoietic stem cell transplant may be a better treatment for multiple
 myeloma.
This is a phase I, dose-escalation study of melphalan and bortezomib followed by a phase II
 study.

 Patients receive melphalan intravenously (IV) continuously on days -5 to -2 and bortezomib IV
 over 3-5 seconds on days -4 and -1. Patients also receive dexamethasone IV on day -1 prior to
 the second dose of bortezomib. Beginning two days after completion of melphalan infusion,
 patients undergo autologous hematopoietic stem cell transplant. Eligible patients may undergo
 a second transplant 2-4 months after completion of the first transplant.

 After completion of study treatment, patients are followed up monthly for at least 1 year and
 then every 3-6 months thereafter.
Inclusion Criteria:

 -  Patients with symptomatic active multiple myeloma requiring treatment, including those
 whose prior smoldering myeloma progressed to symptomatic disease requiring
 chemotherapy; both newly diagnosed and previously treated patients are eligible for
 the study

 -  Presence of quantifiable M-component of immunoglobulin G (IgG), IgA, IgD, or IgE
 and/or urinary kappa or lambda light chain or Bence Jones protein, in order to
 evaluate response; non-secretory patients are eligible provided the patient has > 20%
 plasmacytosis or multiple (> 3) focal plasmacytomas on magnetic resonance imaging
 (MRI) or diffuse hyperintense signal on short tau inversion recovery (STIR) weighted
 images

 -  Performance status of 0-2 based on Southwest Oncology Group (SWOG) criteria; patients
 with a poor performance status (3-4) are also eligible after having improved their
 performance to 0-2

 -  No significant co-morbid medical conditions; no uncontrolled life threatening
 infection

 -  Patient evaluation should be done within 35 days prior to registration; signed
 informed consent should be obtained from all patients in accordance with institutional
 and federal guidelines

 Exclusion Criteria:

 -  Patients with a history of recent (< 6 months) myocardial infarction, unstable angina,
 difficult to control congestive heart failure, uncontrolled hypertension, difficult to
 control significant cardiac arrhythmias, or arrhythmia associated with prolonged QT
 interval; left ventricular ejection fraction by echocardiogram or multi gated
 acquisition scan (MUGA) < 45% assessed within 35 days prior to study registration

 -  Patients with a history of moderate to severe chronic obstructive and/or restrictive
 pulmonary disease, with a forced expiratory volume in 1 second (FEV1) or forced vital
 capacity (FVC) < 50% of the predicted values; diffusing capacity of the lung for
 carbon monoxide (DLCO) < 50%; partial pressure of oxygen (P02) < 70 mmHg

 -  Patients with a prior history of malignancy except for adequately treated basal cell
 or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
 patient has been disease free for at least three years

 -  Pregnant or nursing women; women of child-bearing potential must have a negative
 pregnancy documented within one week of registration; women/men of reproductive
 potential may not participate unless they have agreed to use two forms of effective
 contraceptive method

 -  Human immunodeficiency virus (HIV) positive patients

 -  Transaminases > 2 x normal values or bilirubin > 2 x normal values; prior history of
 chronic liver disease

 -  Patients with renal failure on dialysis

 -  Active uncontrolled infection

 -  History of significant psychiatric illness