Study of Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.
Study of Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.
The purpose of this research study is to determine the safest dose of topotecan when given in
 a high dose before a stem cell transplant; topotecan will be given with melphalan.
The stem cells being transplanted are cells found in the bone marrow and blood that are
 responsible for making red blood cells, white blood cells, and platelets. The stem cells are
 collected by a process called leukapheresis and will be frozen for later use. After receiving
 the chemotherapy drugs, the stem cells will be thawed and given like a blood transfusion.
 This is called autologous stem cell transplant or rescue. The study doctors will be measuring
 how well the disease responds to the drugs as well as any side effects to the drugs. During
 the course of this study, blood and bone marrow samples will be obtained to measure levels of
 the chemotherapy drugs as well as levels of certain enzymes (proteins).

 The staff of the Blood and Marrow Transplant program will continue to collect information
 about the participant's disease and its treatment for the rest of their life.
Inclusion Criteria:

 -  Multiple Myeloma Criteria = Newly diagnosed with drug sensitive disease (>50% tumor
 response to standard chemotherapy) and poor prognostic indicators, such as
 Salmon-Durie stage III, serum b-2-microglobulin >3.0 mg/L, high proliferative fraction
 or hypodiploidy. Relapsed patients after a response to standard chemotherapy. Patients
 with primary refractory disease. Patients with non-secretory multiple myeloma are
 eligible for enrollment on this study. They will be followed for toxicity, survival
 and molecular endpoint analyses, but will not be followed for response. Patients with
 plasma cell leukemia, either occurring de novo or arising from existing multiple
 myeloma, are ineligible for this study.

 -  Patients greater than or equal to 18 years of age are eligible.

 -  Patients must have histologically confirmed diagnosis by a pathologic review at the H.
 Lee Moffitt Cancer Center and Research Institute.

 -  Patients must have undergone a complete psychosocial evaluation and been considered
 capable of compliance.

 -  Patients willing and able to receive palifermin (young cohort only)

 Exclusion Criteria:

 -  Patients with a diffusing lung capacity oxygenation (DLCO) less than 50% (adjusted) of
 normal or with symptomatic obstructive or restrictive disease are ineligible.

 -  Patients with a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance
 of less than 40 ml/minute. Creatinine clearance can be measured or calculated.
 Patients with renal dysfunction secondary to multiple myeloma may be enrolled at the
 discretion of the principal investigator. However, patients on hemodialysis or
 peritoneal dialysis are ineligible.

 -  Patients with a total bilirubin greater than 2.0 mg/dL and serum glutamate
 oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT)
 greater than two and a half times normal (unless due to primary malignancy), or a
 history of severe hepatic dysfunction are ineligible.

 -  Patients who have evidence of severe cardiac dysfunction are ineligible. A gated blood
 pool (MUGA) scan must show an ejection fraction of at least 50%. Patients must be free
 of major heart disease. Patients are ineligible if they have received a total dose of
 doxorubicin of greater than 450 mg/m2 (or daunorubicin equivalent) unless the left
 ventricular ejection fraction by MUGA scan is at least 50%. Patients must not be
 taking nitroglycerin preparations for angina pectoris or antiarrhythmic drugs for
 major ventricular dysrhythmias. Patients with essential hypertension controlled with
 medications are eligible for study. Any patient with congenital or acquired heart
 disease or cardiac arrhythmias will have a cardiology consult and evaluation.

 -  Patients with active infections are ineligible.

 -  Patients who are HIV antibody positive are ineligible.

 -  Patients with active leptomeningeal involvement are ineligible. Patients with a
 history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or
 signs are eligible provided the CSF is now free of disease on lumbar puncture and MRI
 of the brain shows no tumor involvement. Patients with severe symptomatic central
 nervous system (CNS) disease of any etiology are ineligible.

 -  Patients with uncontrolled insulin-dependent diabetes mellitus or uncompensated major
 thyroid or adrenal dysfunction are ineligible.

 -  Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of > or
 = 2 are ineligible. Patients with ECOG performance status 2 to 3 secondary to bone
 pain may be enrolled at the discretion of the institutional investigator. Patients
 with ECOG performance status 2 to 3 secondary to a potentially reversible
 disease-related problem may be enrolled at the discretion of the institutional
 investigator.

 -  Patients who are pregnant or lactating are ineligible.

 -  Patients with any previous malignancy other than non-melanoma skin cancer are
 ineligible, unless the patient is without evidence of disease > or = 5 years after the
 treatment for the cancer was completed.

 -  Patients previously treated with topotecan or any other topoisomerase I inhibitor.